US20220403380A1 - RNA Interactome of Polycomb Repressive Complex 1 (PRC1)

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Abstract

Description

Claims

US20220403380A1

Publication number: US20220403380A1
Application number: US17/038,425
Authority: US
Inventors: Jeannie T. Lee; Michael Rosenberg; Barry Kesner
Original assignee: General Hospital Corp
Current assignee: General Hospital Corp
Priority date: 2015-03-17
Filing date: 2020-09-30
Publication date: 2022-12-22
Also published as: US20180320175A1; US10900036B2; EP3271460A4; US20230348908A1; WO2016149455A3; WO2016149455A2; EP3271460A2

This invention relates to polycomb-associated RNAs, libraries and fragments of those RNAs, inhibitory nucleic acids and methods and compositions for targeting RNAs, and methods of use thereof.

CLAIM OF PRIORITY

This application is a continuation of U.S. patent application Ser. No. 15/558,974, filed Sep. 15, 2017, which is a U.S. National Phase Application under 35 U.S.C. § 371 of International Patent Application No. PCT/US2016/022778, filed on Mar. 17, 2016, which claims the benefit of U.S. Provisional Patent Application Ser. No. 62/134,361, filed on Mar. 17, 2015. The entire contents of the foregoing are hereby incorporated by reference.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with Government support under Grant No. RO1-DA36895 awarded by the National Institutes of Health. The Government has certain rights in the invention.

TECHNICAL FIELD

This invention relates to the RNA interactome of Polycomb Repressive Complex 1 (PRC1) and methods of using inhibitory nucleic acids that bind RNAs and inhibit the PRC1-RNA interaction to modulate gene expression.

BACKGROUND

Transcriptome analyses have suggested that, although only 1-2% of the mammalian genome is protein-coding, 70-90% is transcriptionally active (Carninci et al., 2005; Kapranov et al., 2007; Mercer et al., 2009). Ranging from 100 nt to >100 kb, these transcripts are largely unknown in function, may originate within or between genes, and may be conserved and developmentally regulated (Kapranov et al., 2007; Guttman et al., 2009). Recent discoveries argue that a subset of these transcripts play crucial roles in epigenetic regulation.
RNA-mediated recruitment is especially attractive for Polycomb proteins. First identified in Drosophila as homeotic regulators, Polycomb proteins are conserved from flies to mammals and control many aspects of development (Ringrose and Paro, 2004; Boyer et al., 2006; Lee et al., 2006; Schuettengruber et al., 2007; Pietersen and van Lohuizen, 2008; Schwartz and Pirrotta, 2008).
Polycomb Repressive Complex 1 (PRC1) is the enzymatic complex that ubiquitylates histone H2A at lysine 119 (H2AK119Ub). In mammals, it is composed of multiple variable subunits, including (1) the catalytic subunit, Ring1b or Ring1a; (2) Bmi1 (which can be PCGF1, PCGF2, PCGF3, PCGF5, or PCGF6); (3) PH1 (or PH2, PH3); and (4) CBX2, 4, 6, 7, or 8. Action of PRC1 on chromatin results in chromatin compaction and transcriptional repression. The classical PRC1 complex exists in two forms in which either CBX and MPH or RYBP subunits associate with the catalytic core subunits RING1A/B and PCGF2/4. The PRC1 interacting protein, SCMLH1/2/3, is only weakly associated/substoichiometric and is considered an accessory factor, rather than a core component. The RanBP-ZF domain present in RYBP/YAF2 has an RNA binding function in some related proteins but apparently not in RYBP/YAF2. See, e.g., Brockdorff, RNA 19:429-442 (2013); Yap et al., Mol Cell. 38(5):662-74 (2010).
Although PRC1 binds thousands of sites in the mammalian genome, how PRC1 is targeted to chromatin has remained a mystery. YY1 and the H3K27me3 chromatin mark may recruit PRC1 in some contexts, but they are unlikely to be the general or only mechanisms. RNA-mediated targeting is another potential mechanism. PRC1 is known to interact with at least one RNA, ANRIL, likely via the chromodomain (CD) of the CBX7 protein (Yap et al., Mol Cell. 38(5):662-74 (2010)). ANRIL is an antisense non-coding RNA (ncRNA) at the INK4b/ARF/INK4a locus (Pasmant et al., Cancer Res 67: 3963-3969 (2007)). How many RNAs interact with PRC1 and whether they are a general recruiting tool for PRC1 has not previously been determined.

SUMMARY

A new ‘denaturing’ CLIP-seq method was developed using the biotin-avidin method, which enables washes in high salt and urea (i.e., protein denaturing conditions). Because the exemplified system includes two protein tags, FLAG and biotin, purification can be performed with either tag or conducted as a tandem affinity purification (e.g., FLAG purification first, followed by biotin pulldown). For the denaturing method, the biotin tag is preferably used. During CLIP, because the interacting RNAs are UV-crosslinked to RNA-binding proteins in a covalent fashion, the RNA-protein interactions survive the wash conditions, whereas nonspecific, low-affinity interactions are not preserved. These methods were used to identify genome-wide pools of polycomb repressive complex 1 (PRC1)-interacting RNAs (referred to herein as the “PRC1 transcriptome” or “PRC1 RNA interactome”) in several cell types, including embryonic stem cells and human fibroblast cells.
The results of the studies described herein demonstrated that PRC1 binds both noncoding RNA and coding RNA. The transcriptome includes antisense, intergenic, and promoter-associated transcripts, as well as many unannotated RNAs. A large number of transcripts occur within imprinted regions, oncogene and tumor suppressor loci, and stem-cell-related bivalent domains. Further evidence is provided that inhibitory oligonucleotides that specifically bind to these PRC1-interacting RNAs can successfully modulate gene expression in a variety of separate and independent examples, presumably by inhibiting PRC1-associated effects. PRC1 binding sites can be classified into several groups, including (i) 3′ untranslated region [3′ UTR], (ii) promoter-associated, (iii) gene body, (iv) antisense, and (v) intergenic. Inhibiting the PRC1-RNA interactions can lead to either activation or repression, depending on context.
Also provided herein are methods for isolating RNA sequences that interact with a selected protein, e.g., with chromatin complexes, in a cell; the methods include providing a cell expressing (i) a biotin ligase, e.g., BirA, and (ii) the protein of interest comprising a biotinylation sequence; exposing the cells to UV-crosslinking; lysing the cells, isolating protein-RNA complexes from the lysed cells, e.g., using avidin purification, e.g., streptavidin beads; washing the complexes in protein-denaturing conditions, e.g., high salt and detergent, e.g., using 8 M urea+0.1% SDS; and isolating the protein-RNA complexes.
In one aspect, described herein are methods for isolating RNA sequences that interact with a selected protein, e.g., with chromatin complexes. The methods include providing a cell expressing (i) a biotin ligase, e.g., BirA, and (ii) the protein of interest comprising a biotinylation sequence; exposing the cells to UV-crosslinking to crosslink the proteins to RNA, to create protein-RNA complexes; lysing the cells to obtain a sample comprising the protein-RNA complexes; isolating protein-RNA complexes from the lysed cells, e.g., using avidin purification, e.g., streptavidin beads; washing the complexes in protein-denaturing conditions, e.g., high salt and detergent, e.g., using 8 M urea+0.1% SDS; and isolating the protein-RNA complexes.
In some embodiments, the methods include optionally preparing a plurality of validated cDNAs complementary to the pool of ribonucleic acids (RNAs) that bind to the protein of interest; these methods include synthesizing DNA complementary to the RNAs to provide an initial population of cDNAs; PCR-amplifying, if necessary, using strand-specific primers; purifying the initial population of cDNAs to obtain a purified population of cDNAs that are at least about 20 nucleotides (nt) in length, e.g., at least 25, 50, 75, 100, 150, 200, or 250 nt in length; sequencing at least part or substantially all of the purified population of cDNAs; aligning reads to a reference genome and retaining only those that are aligned; selecting high-confidence cDNA sequences, optionally, based on criteria that (1) the candidate transcript has a minimum read density in reads per kilobase per million reads (RPKM) terms (e.g., above a desired threshold); and/or (2) the candidate transcript is enriched in the wildtype library versus a suitable control library (such as an IgG pulldown library or a protein-null pulldown library); thereby preparing the plurality of cDNAs. In some embodiments, the cDNAs are synthesized using strand-specific adaptors.
In some embodiments, the method is used to prepare a library representing a transcriptome associated with the protein of interest.
In some embodiments, the methods further include sequencing substantially all of the cDNAs.
In another aspect the invention features an inhibitory nucleic acid that specifically binds to, or is complementary to a region of an RNA that is known to bind to Polycomb repressive complex 1 (PRC1), wherein the sequence of the region is selected from the group consisting of SEQ ID NOs:1 to 5893 (human), 5894 to 17415 (human), and 17416 to 36368 (mouse) as set forth in Tables 1-3. Without being bound by a theory of invention, these inhibitory nucleic acids are able to interfere with the binding of and function of PRC1, by preventing recruitment of PRC1 to a specific chromosomal locus. For example, data herein shows that a single administration of inhibitory nucleic acids designed to specifically bind a RNA can alter expression of a gene associated with the RNA. Data provided herein also indicate that putative ncRNA binding sites for PRC1 show no conserved primary sequence motif, making it possible to design specific inhibitory nucleic acids that will interfere with PRC1 interaction with a single ncRNA, without generally disrupting PRC1 interactions with other ncRNAs. Further, data provided herein support that RNA can recruit PRC1 in a cis fashion, repressing gene expression at or near the specific chromosomal locus from which the RNA was transcribed, thus making it possible to design inhibitory nucleic acids that inhibit the function of PRC1 and increase the expression of a specific target gene.
In some embodiments, the inhibitory nucleic acid is provided for use in a method of modulating expression of a “gene targeted by the PRC1-binding RNA” (e.g., an intersecting or nearby gene, as set forth in Tables 1-3 below), meaning a gene whose expression is regulated by the PRC1-binding RNA. The term “PRC1-binding RNA” or “RNA that binds PRC1” is used interchangeably with “PRC1-associated RNA” and “PRC1-interacting RNA”, and refers to an RNA transcript or a region thereof (e.g., a Peak as described below) that binds the PRC1 complex, directly or indirectly. Such binding may be determined by dCLIP-SEQ techniques described herein using a component of the PRC1 complex, e.g., PRC1 itself. SEQ ID NOs: 1 to 5893 represent human RNA sequences containing portions that have been experimentally determined to bind PRC1 using the dCLIP-seq method described herein; SEQ ID NOs: 17416 to 36368 represent murine RNA sequences containing portions that have been experimentally determined to bind PRC1 using the dCLIP-seq method described herein; and SEQ ID NOs: 5894 to 17415 represent or human RNA sequences corresponding to the murine RNA sequences.
Such methods of modulating gene expression may be carried out in vitro, ex vivo, or in vivo. Tables 1-3 display genes targeted by the PRC1-binding RNA; the SEQ ID NOS: of the PRC1-associated RNA are set forth in the same row as the gene name. In some embodiments, the inhibitory nucleic acid is provided for use in a method of treating disease, e.g. a disease category as described herein. The treatment may involve modulating expression (either up or down) of a gene targeted by the PRC1-binding RNA, preferably upregulating gene expression. The inhibitory nucleic acid may be formulated as a sterile composition for parenteral administration. It is understood that any reference to uses of compounds throughout the description contemplates use of the compound in preparation of a pharmaceutical composition or medicament for use in the treatment of a disease. Thus, as one nonlimiting example, this aspect of the invention includes use of such inhibitory nucleic acids in the preparation of a medicament for use in the treatment of disease, wherein the treatment involves upregulating expression of a gene targeted by the PRC1-binding RNA.
Diseases, disorders or conditions that may be treated according to the invention include cardiovascular, metabolic, inflammatory, bone, neurological or neurodegenerative, pulmonary, hepatic, kidney, urogenital, bone, cancer, and/or protein deficiency disorders.
In a related aspect, the invention features a process of preparing an inhibitory nucleic acid that modulates gene expression, the process comprising the step of synthesizing an inhibitory nucleic acid of between 5 and 40 bases in length, or about 8 to 40, or about 5 to 50 bases in length, optionally single stranded, that specifically binds, or is complementary to, an RNA sequence that has been identified as binding to PRC1, optionally an RNA of any of Tables 1-3 or any one of SEQ ID NOs: 1 to 5893, or 5894 to 17415, or 17416 to 36368. This aspect of the invention may further comprise the step of identifying the RNA sequence as binding to PRC1, optionally through the dCLIP-seq method described herein.
In a further aspect of the present invention a process of preparing an inhibitory nucleic acid that specifically binds to an RNA that binds to Polycomb repressive complex 1 (PRC1) is provided, the process comprising the step of designing and/or synthesizing an inhibitory nucleic acid of between 5 and 40 bases in length, or about 8 to 40, or about 5 to 50 bases in length, optionally single stranded, that specifically binds to an RNA sequence that binds to PRC1, optionally an RNA of any of Tables 1-3 or any one of SEQ ID NOs: 1 to 5893, or 5894 to 17415, or 17416 to 36368.
In some embodiments prior to synthesizing the inhibitory nucleic acid the process further comprises identifying an RNA that binds to PRC1.
In some embodiments the RNA has been identified by a method involving identifying an RNA that binds to PRC1.
In some embodiments the inhibitory nucleic acid is at least 80% complementary to a contiguous sequence of between 5 and 40 bases, or about 8 to 40, or about 5 to 50 bases in said RNA sequence that binds to PRC1. In some embodiments the sequence of the designed and/or synthesized inhibitory nucleic acid is based on a said RNA sequence that binds to PRC1, or a portion thereof, said portion having a length of from 5 to 40 contiguous base pairs, or about 8 to 40 bases, or about 5 to 50 bases.
In some embodiments the sequence of the designed and/or synthesized inhibitory nucleic acid is based on a nucleic acid sequence that is complementary to said RNA sequence that binds to PRC1, or is complementary to a portion thereof, said portion having a length of from 5 to 40 contiguous base pairs, or about 8 to 40 base pairs, or about 5 to 50 base pairs.
The designed and/or synthesized inhibitory nucleic acid may be at least 80% complementary to (optionally one of at least 90%, 95%, 96%, 97%, 98%, 99% or 100% complementary to) the portion of the RNA sequence to which it binds or targets, or is intended to bind or target. In some embodiments it may contain 1, 2 or 3 base mismatches compared to the portion of the target RNA sequence or its complement respectively. In some embodiments it may have up to 3 mismatches over 15 bases, or up to 2 mismatches over 10 bases.
The inhibitory nucleic acid or portion of RNA sequence that binds to PRC1 may have a length of one of at least 8 to 40, or 10 to 50, or 5 to 50, or 5 to 40 bases, e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 bases. Where the inhibitory nucleic acid is based on an RNA sequence that binds to PRC1, a nucleic acid sequence that is complementary to said RNA sequence that binds to PRC1 or a portion of such a sequence, it may be based on information about that sequence, e.g. sequence information available in written or electronic form, which may include sequence information contained in publicly available scientific publications or sequence databases.
In some embodiments, the isolated single stranded oligonucleotide is of 5 to 40 nucleotides in length and has a region of complementarity that is complementary with at least 5 contiguous nucleotides of the PRC1-binding RNA that inhibits expression of the target gene, wherein the oligonucleotide is complementary to and binds specifically within a PRC1-binding region of the PRC1-binding RNA and interferes with binding of PRC1 to the PRC1-binding region without inducing degradation of the PRC1-binding RNA (e.g., wherein the PRC1-binding region has a nucleotide sequence identified using a denaturing cross-linking immunoprecipitation procedure using an a biotin-tagged PRC1 as described herein), and without interfering with binding of PRC2 to a PRC2-binding region of the RNA (as described in WO 2012/087983 or WO 2012/065143, wherein the PRC2-binding region has a nucleotide sequence protected from nucleases during an RNA immunoprecipitation procedure using an antibody directed against PRC2), optionally wherein the PRC1-binding RNA is transcribed from a sequence of the chromosomal locus of the target gene, and optionally wherein a decrease in recruitment of PRC1 to the target gene in the cell following delivery of the single stranded oligonucleotide to the cell, compared with an appropriate control cell to which the single stranded oligonucleotide has not been delivered, indicates effectiveness of the single stranded oligonucleotide.
Where the design and/or synthesis involves design and/or synthesis of a sequence that is complementary to a nucleic acid described by such sequence information the skilled person is readily able to determine the complementary sequence, e.g. through understanding of Watson-Crick base pairing rules which form part of the common general knowledge in the field.
In the methods described above the RNA that binds to PRC1 may be, or have been, identified, or obtained, by a method that involves identifying RNA that binds to PRC1.
Such methods may involve the following steps: providing a sample containing nuclear ribonucleic acids, contacting the sample with an agent that binds specifically to PRC1 or a subunit thereof, allowing complexes to form between the agent and protein in the sample, partitioning the complexes, synthesizing nucleic acid that is complementary to nucleic acid present in the complexes.
If necessary, the method may further comprise the steps of amplifying the synthesized nucleic acid, and/or purifying the nucleic acid (or amplified nucleic acid), and/or sequencing the nucleic acids so obtained, and/or filtering/analysing the nucleic acids so obtained to identify high-probability PRC1 (or subunit thereof)-interacting transcripts.
In one embodiment the method involves the dCLIP-Seq method described herein.
In accordance with the above, in some embodiments the RNA that binds to PRC1 may be one that is known to bind PRC1, e.g. information about the sequence of the RNA and/or its ability to bind PRC1 is available to the public in written or electronic form allowing the design and/or synthesis of the inhibitory nucleic acid to be based on that information. As such, an RNA that binds to PRC1 may be selected from known sequence information and used to inform the design and/or synthesis of the inhibitory nucleic acid.
In other embodiments the RNA that binds to PRC1 may be identified as one that binds PRC1 as part of the method of design and/or synthesis.
In preferred embodiments design and/or synthesis of an inhibitory nucleic acid involves manufacture of a nucleic acid from starting materials by techniques known to those of skill in the art, where the synthesis may be based on a sequence of an RNA (or portion thereof) that has been selected as known to bind to Polycomb repressive complex 2.
Methods of design and/or synthesis of an inhibitory nucleic acid may involve one or more of the steps of:
Identifying and/or selecting a portion of an RNA sequence that binds to PRC1 (e.g., as shown in Tables 1-3);
Designing a nucleic acid sequence having a desired degree of sequence identity or complementarity to an RNA sequence that binds to PRC1 or a portion thereof;
Synthesizing a nucleic acid to the designed sequence;
Mixing the synthesized nucleic acid with at least one pharmaceutically acceptable diluent, carrier or excipient to form a pharmaceutical composition or medicament.
Inhibitory nucleic acids so designed and/or synthesized may be useful in method of modulating gene expression as described herein.
As such, the process of preparing an inhibitory nucleic acid may be a process that is for use in the manufacture of a pharmaceutical composition or medicament for use in the treatment of disease, optionally wherein the treatment involves modulating expression of a gene targeted by the RNA binds to PRC1.
Thus, provided herein are methods for isolating RNA sequences that interact with a selected protein, e.g., with chromatin complexes, in a cell. The methods include providing a cell expressing (i) a biotin ligase, e.g., BirA, and (ii) the protein of interest comprising a biotinylation sequence; exposing the cells to UV-crosslinking; lysing the cells, isolating protein-RNA complexes from the lysed cells, e.g., using avidin purification, e.g., streptavidin beads; washing the complexes in protein-denaturing conditions, e.g., high salt and detergent, e.g., using 8 M urea+0.1% SDS; and isolating the protein-RNA complexes. In some embodiments, the methods include labelling the RNA in the RNA-protein complexes, e.g., by phosphorylation using ³²P-ATP. In some embodiments, the methods include purifying the RNA-protein complexes, preparing cDNA from the RNA, and deep sequencing the cDNA to identify the RNA sequences bound to the protein.
Also provided are kits for use in the methods described herein; these kits include an expression vector comprising a sequence encoding a biotin ligase, and an expression vector comprising a sequence encoding a biotinylation sequence, and optionally one or more buffers. In some embodiments, the the buffers include one or more of a high stringency denaturing buffer, e.g., comprising 8 M urea (range: 5-10 M, 6-10M, 7-10M, 7-9M, or 7.5-8.5M) plus 0.1% SDS (range: 0.0-2.0%); a wash buffer (e.g., PBS+2% SDS; and a high salt wash buffer (e.g., PBS+750 mM NaCl+1% NP40+0.5% NaDeoxycholate+0.1% SDS).
In yet another aspect, the invention provides isolated nucleic acids comprising a sequence referred to in any of Tables 1-3, or a fragment comprising at least 20 nt thereof. In some or any embodiments, the invention provides an isolated nucleic acid comprising (a) an RNA sequence as set forth in Tables 1-3 that targets a proto-oncogene or oncogene as set forth in Tables 1-3, or (b) a fragment of (a) that is at least 20 bases in length that retains PRC1-binding activity, or (c) a derivative of (a) or (b) that is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% homologous thereto, or (d) a nucleic acid of (a), (b), or (c) in which one or more bases has been replaced with a base of similar base-pairing capacity, such as replacing U with T. In preferred embodiments, the isolated nucleic acid of (a), (b) or (c) is for use in a method of decreasing expression of an oncogene. In some embodiments, the isolated nucleic acid is synthetic. In some embodiments, the isolated RNA comprises a SEQ ID NO. associated with Pvt1 in Tables 1-3. Pvt1 is known in the art to be disrupted in some cases of Burkitt's lymphoma as well as in plasmacytomas (e.g., by translocations from another chromosome). Therefore, Pvt1 is likely to act by targeting PRC1 to c-Myc in order to repress its expression. Accordingly, exogenous administration of any of the RNA sequences associated with Pvt1 in Tables 1-3, or inhibitory nucleic acids complementary thereto, could rescue Pvt1 loss-of-function phenotypes contributing to various cancers.
In a further aspect, the invention provides methods for decreasing expression of an oncogene in a cell. In some embodiments, the methods include contacting the cell with a PRC1-binding fragment described in any of Tables 1-3, or a nucleic acid sequence that is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% homologous to a PRC1-binding fragment as referred to in any of Tables 1-3. In exemplary methods, the RNA a nucleic acid in which one or more bases has been replaced with a base of similar base-pairing capacity, such as replacing U with T. PRC1-binding fragments of murine or orthologous ncRNAs, including human ncRNA, which retain the ncRNA's ability to bind PRC1, are contemplated.
In yet another aspect, the invention features methods for increasing expression of a tumor suppressor in a mammal, e.g. human, in need thereof. The methods include administering to said mammal an inhibitory nucleic acid that specifically binds, or is complementary, to a human PRC1-interacting RNA corresponding to a tumor suppressor locus of any of Tables 1-3 or a human RNA corresponding to an imprinted gene of any of Tables 1-3, or a related naturally occurring RNA that is othologous or at least 90%, (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%%, or 100%) identical over at least 15 (e.g., at least 20, 21, 25, 30, 100) nucoleobases thereof, in an amount effective to increase expression of the tumor suppressor or growth suppressing gene. It is understood that one method of determining human orthologous RNA that corresponds to murine RNA is to identify a corresponding human sequence at least 90% identical (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical) to at least 15 nucleobases of the murine sequence (or at least 20, 21, 25, 30, 40, 50, 60, 70, 80, 90 or 100 nucleobases).
In an additional aspect, the invention provides methods for inhibiting or suppressing tumor growth in a mammal, e.g. human, with cancer, comprising administering to said mammal an inhibitory nucleic acid that specifically binds, or is complementary, to a human PRC1-interacting RNA corresponding to a tumor suppressor locus of any of Tables 1-3, or a human RNA corresponding to an imprinted gene of any of Tables 1-3, or a related naturally-occurring RNA that is orthologous or at least 90%, (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical over at least 15 (e.g., at least 20, 21, 25, 30, 50, 70, 100) nucleobases thereof, in an amount effective to suppress or inhibit tumor growth.
In another aspect, the invention features methods for treating a mammal, e.g., a human, with cancer comprising administering to said mammal an inhibitory nucleic acid that specifically binds, or is complementary, to a human RNA corresponding to a tumor suppressor locus of any of Tables 1-3, or a human RNA corresponding to an imprinted gene of Tables 1-3, or a related naturally occurring RNA that is orthologous or at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identical over at least 15 (e.g., at least 20, 21, 25, 30, 50, 70, 100) nucleobases thereof, in a therapeutically effective amount.
Also provided herein are inhibitory nucleic acids that specifically bind, or are complementary to, a region of an RNA that is known to bind to Polycomb repressive complex 1 (PRC1), wherein the sequence of the region is selected from the group consisting of SEQ ID NOs:1 to 5893 (human), 5894 to 17415 (human), and 17416 to 36368 (mouse) as set forth in Tables 1-3, for use in the treatment of disease, wherein the treatment involves modulating expression of a gene targeted by the RNA, wherein the inhibitory nucleic acid is between 5 and 40 bases in length, and wherein the inhibitory nucleic acid is formulated as a sterile composition.
Further described herein are processs for preparing an inhibitory nucleic acid that specifically binds, or is complementary to, an RNA that is known to bind to Polycomb repressive complex 1 (PRC1), selected from the group consisting of SEQ ID NOs:1 to 5893 (human), 5894 to 17415 (human), and 17416 to 36368 (mouse) as set forth in Tables 1-3; the processes include the step of designing and/or synthesizing an inhibitory nucleic acid of between 5 and 40 bases in length, optionally single stranded, that specifically binds to a region of the RNA that binds PRC1.
In some embodiments, the sequence of the designed and/or synthesized inhibitory nucleic acid is a nucleic acid sequence that is complementary to said RNA sequence that binds to PRC1, or is complementary to a portion thereof, said portion having a length of from 5 to 40 contiguous base pairs.
In some embodiments, the inhibitory nucleic acid is for use in the manufacture of a pharmaceutical composition or medicament for use in the treatment of disease, optionally wherein the treatment involves modulating expression of a gene targeted by the RNA binds to PRC1.
In some embodiments, the modulation is increasing expression of a gene and the region of the RNA that binds PRC1 can be in intergenic space mapping to a noncoding RNA, antisense to the coding gene, or in the promoter, 3′UTR, 5′UTR, exons, and introns of a coding gene.
In some embodiments, the modulation is decreasing expression of a gene and the region of the RNA that binds PRC1 can be in intergenic space mapping to a noncoding RNA, antisense to the coding gene, or in the promoter, 3′UTR, 5′UTR, exons, and introns of a coding gene.
In some embodiments, the modulation is to influence gene expression by altering splicing of a gene and the region of the RNA that binds PRC1 can be in intergenic space mapping to a noncoding RNA, antisense to the coding gene, or in the promoter, 3′UTR, 5′UTR, exons, and introns of a coding gene.
Also provided herein are sterile compositions comprising an inhibitory nucleic acid that specifically binds, or is complementary to, an RNA sequence of any one of SEQ ID NOs:1 to 5893 (human), 5894 to 17415 (human), and 17416 to 36368 (mouse) and is capable of modulating expression of a gene targeted by the RNA as set forth in Tables 1-3.
In some embodiments, the composition is for parenteral administration. In some embodiments, the RNA sequence is in the 3′UTR of a gene, and the inhibitory nucleic acid is capable of upregulating or downregulating expression of a gene targeted by the RNA.
Also provided herein is an inhibitory nucleic acid for use in the treatment of disease, wherein said inhibitory nucleic acid specifically binds, or is complementary to, an RNA sequence of any one of SEQ ID NOs:1 to 5893 (human) or 5894 to 17415 (human), and wherein the treatment involves modulating expression of a gene targeted by the RNA according to Tables 1-3.
The present disclosure also provides methods for modulating gene expression in a cell or a mammal comprising administering to the cell or the mammal an inhibitory nucleic acid that specifically binds, or is complementary to, an RNA sequence of any one of SEQ ID NOs:1 to 5893 (human) or 5894 to 17415 (human) or 17416 to 36368 (mouse), in an amount effective for modulating expression of a gene targeted by the RNA according to Table 1-3.
In addition, provided herein are inhibitory nucleic acids of about 5 to 50 bases in length that specifically bind, or are complementary to, a fragment of at least five consecutive bases within any of SEQ ID NOs:1 to 5893 (human) or 5894 to 17415 (human) or 17416 to 36368 (mouse), optionally for use in the treatment of disease, wherein the treatment involves modulating expression of a gene targeted by the RNA.
In addition, provided are methods for modulating expression of a gene comprising administering to a mammal an inhibitory nucleic acid as described herein in an amount effective for modulating expression of a gene targeted by the RNA as set forth in Tables 1-3.
In some embodiments, the modulation is upregulating or downregulating gene expression, optionally wherein the gene targeted by the RNA is selected from the group set forth in Tables 1-3, and wherein the RNA sequence is listed in the same row as the gene.
In some embodiments, the inhibitory nucleic acid is 5 to 40 bases in length (optionally 12-30, 12-28, or 12-25 bases in length).
In some embodiments, the inhibitory nucleic acid is 10 to 50 bases in length.
In some embodiments, the inhibitory nucleic acid comprises a base sequence at least 90% complementary to at least 10 bases of the RNA sequence.
In some embodiments, the inhibitory nucleic acid comprises a sequence of bases at least 80% or 90% complementary to, e.g., at least 5-30, 10-30, 15-30, 20-30, 25-30 or 5-40, 10-40, 15-40, 20-40, 25-40, or 30-40 bases of the RNA sequence.
In some embodiments, the inhibitory nucleic acid comprises a sequence of bases with up to 3 mismatches (e.g., up to 1, or up to 2 mismatches) in complementary base pairing over 10, 15, 20, 25 or 30 bases of the RNA sequence.
In some embodiments, the inhibitory nucleic acid comprises a sequence of bases at least 80% complementary to at least 10 bases of the RNA sequence.
In some embodiments, the inhibitory nucleic acid comprises a sequence of bases with up to 3 mismatches over 15 bases of the RNA sequence.
In some embodiments, the inhibitory nucleic acid is single stranded.
In some embodiments, the inhibitory nucleic acid is double stranded.
In some embodiments, the inhibitory nucleic acid comprises one or more modifications comprising: a modified sugar moiety, a modified internucleoside linkage, a modified nucleotide and/or combinations thereof.
In some embodiments, the inhibitory nucleic acid is an antisense oligonucleotide, LNA molecule, PNA molecule, ribozyme or siRNA.
In some embodiments, the inhibitory nucleic acid is double stranded and comprises an overhang (optionally 2-6 bases in length) at one or both termini.
In some embodiments, the inhibitory nucleic acid is selected from the group consisting of antisense oligonucleotides, ribozymes, external guide sequence (EGS) oligonucleotides, siRNA compounds, micro RNAs (miRNAs); small, temporal RNAs (stRNA), and single- or double-stranded RNA interference (RNAi) compounds.
In some embodiments, the RNAi compound is selected from the group consisting of short interfering RNA (siRNA); or a short, hairpin RNA (shRNA); small RNA-induced gene activation (RNAa); and small activating RNAs (saRNAs).
In some embodiments, the antisense oligonucleotide is selected from the group consisting of antisense RNAs, antisense DNAs, and chimeric antisense oligonucleotides.
In some embodiments, the modified internucleoside linkage comprises at least one of: alkylphosphonate, phosphorothioate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethyl ester, or combinations thereof.
In some embodiments, the modified sugar moiety comprises a 2′-O-methoxyethyl modified sugar moiety, a 2′-methoxy modified sugar moiety, a 2′-O-alkyl modified sugar moiety, or a bicyclic sugar moiety. In some embodiments, the inhibitory nucleic acids include 2′-OMe, 2′-F, LNA, PNA, FANA, ENA or morpholino modifications.
Further provided are sterile compositions comprising an isolated nucleic acid that is a mouse RNA sequence of any one of any one of SEQ ID NOs:1 to 5893 (human) or 5894 to 17415 (human) or 17416 to 36368 (mouse), or a fragment thereof at least 20 bases in length that retains PRC1-binding activity.
Also provided are isolated nucleic acids for use in a method of decreasing expression of an oncogene, comprising an RNA sequence as set forth in Tables 1-3 that targets a proto-oncogene or oncogene as set forth in Tables 1-3, or a fragment thereof at least 20 bases in length that retains PRC1-binding activity.
In addition, provided are methods for decreasing expression of an oncogene in a cell, the method comprising contacting the cell with an RNA sequence as set forth in Tables 1-3 that targets an oncogene as set forth in Tables 1-3, or a fragment thereof at least 20 bases in length that retains PRC1-binding activity.
Further, provided herein are methods of inducing expression of a target gene in a cell, the method comprising delivering to the cell a single stranded oligonucleotide of 5 to 40 nucleotides in length having a region of complementarity that is complementary with at least 5 contiguous nucleotides of a PRC1-binding RNA that inhibits expression of the target gene, wherein the oligonucleotide is complementary to and binds specifically to the PRC1-binding RNA, and wherein the PRC1-binding RNA is transcribed from a sequence of the chromosomal locus of the target gene.
In some embodiments, the RNA is a non-codingRNA.
In some embodiments, the methods include detecting expression of the PRC1-binding RNA in the cell, wherein expression of the PRC1-binding RNA in the cell indicates that the single stranded oligonucleotide is suitable for increasing expression of the target gene in the cell.
In some embodiments, the methods include detecting a change in expression of the target gene following delivery of the single stranded oligonucleotide to the cell, wherein an increase in expression of the target gene compared with an appropriate control cell indicates effectiveness of the single stranded oligonucleotide.
In some embodiments, the methods include detecting a change in recruitment of PRC1 to the target gene in the cell following delivery of the single stranded oligonucleotide to the cell, wherein a decrease in recruitment compared with an appropriate control cell indicates effectiveness of the single stranded oligonucleotide.
In some embodiments, the cell is in vitro.
In some embodiments, the cell is in vivo.
In some embodiments, at least one nucleotide of the oligonucleotide is a modified nucleotide.
In some embodiments, the PRC1-binding RNA is transcribed from the same strand as the target gene in a genomic region containing the target gene.
In some embodiments, the oligonucleotide has complementarity to a region of the PRC1-binding RNA transcribed from a portion of the target gene corresponding to an exon.
In some embodiments, the oligonucleotide has complementarity to a region of the PRC1-binding RNA transcribed from the same strand as the target gene within a chromosomal region within −2.0 kb to +0.001 kb of the transcription start site of the target gene.
In some embodiments, the oligonucleotide has complementarity to a region of the PRC1-binding RNA transcribed from the opposite strand of the target gene within a chromosomal region within −0.5 to +0.1 kb of the transcription start site of the target gene.
In some embodiments, the oligonucleotide has complementarity to the PRC1-binding RNA in a region of the PRC1-binding RNA that forms a stem-loop structure.
In some embodiments, at least one nucleotide of the oligonucleotide is an RNA or DNA nucleotide.
In some embodiments, at least one nucleotide of the oligonucleotide is a ribonucleic acid analogue comprising a ribose ring having a bridge between its 2′-oxygen and 4′-carbon.
In some embodiments, the ribonucleic acid analogue comprises a methylene bridge between the 2′-oxygen and the 4′-carbon.
In some embodiments, at least one nucleotide of the oligonucleotide comprises a modified sugar moiety.
In some embodiments, the modified sugar moiety comprises a 2′-O-methoxyethyl modified sugar moiety, a 2′-methoxy modified sugar moiety, a 2′-O-alkyl modified sugar moiety, or a bicyclic sugar moiety.
In some embodiments, the oligonucleotide comprises at least one modified internucleoside linkage.
In some embodiments, the at least one modified internucleoside linkage is selected from phosphorothioate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethyl ester, and combinations thereof.
In some embodiments, the oligonucleotide is configured such that hybridization of the single stranded oligonucleotide to the PRC1-binding RNA does not activate an RNAse H pathway in the cell.
In some embodiments, the oligonucleotide is configured such that hybridization of the single stranded oligonucleotide to the PRC1-binding RNA does not induce substantial cleavage or degradation of the PRC1-binding RNA in the cell.
In some embodiments, the oligonucleotide is configured such that hybridization of the single stranded oligonucleotide to the PRC1-binding RNA interferes with interaction of the RNA with PRC1 in the cell.
In some embodiments, the target gene is a protein-coding gene.
In some embodiments, the chromosomal locus of the target gene is an endogenous gene of an autosomal chromosome.
In some embodiments, the cell is a cell of a male subject.
In some embodiments, the oligonucleotide has complementarity to a region of the PRC1-binding RNA transcribed from a portion of the target gene corresponding to an intron-exon junction or an intron.
In some embodiments, the oligonucleotide has complementarity to a region of the PRC1-binding RNA transcribed from a portion of the target gene corresponding to a translation initiation region or a translation termination region.
In some embodiments, the oligonucleotide has complementarity to a region of the PRC1-binding RNA transcribed from a portion of the target gene corresponding to a promoter.
In some embodiments, the oligonucleotide has complementarity to a region of the PRC1-binding RNA transcribed from a portion of the target gene corresponding to a 5′-UTR.
In some embodiments, the oligonucleotide has complementarity to a region of the PRC1-binding RNA transcribed from a portion of the target gene corresponding to a 3′-UTR.
In some or any embodiments, the inhibitory nucleic acid is an oligomeric base compound or oligonucleotide mimetic that hybridizes to at least a portion of the target nucleic acid and modulates its function. In some or any embodiments, the inhibitory nucleic acid is single stranded or double stranded. A variety of exemplary inhibitory nucleic acids are known and described in the art. In some examples, the inhibitory nucleic acid is an antisense oligonucleotide, locked nucleic acid (LNA) molecule, peptide nucleic acid (PNA) molecule, ribozyme, siRNA, antagomirs, external guide sequence (EGS) oligonucleotide, microRNA (miRNA), small, temporal RNA (stRNA), or single- or double-stranded RNA interference (RNAi) compounds. It is understood that the term “LNA molecule” refers to a molecule that comprises at least one LNA modification; thus LNA molecules may have one or more locked nucleotides (conformationally constrained) and one or more non-locked nucleotides. It is also understood that the term “LNA” includes a nucleotide that comprises any constrained sugar that retains the desired properties of high affinity binding to complementary RNA, nuclease resistance, lack of immune stimulation, and rapid kinetics. Exemplary constrained sugars include those listed below. Similarly, it is understood that the term “PNA molecule” refers to a molecule that comprises at least one PNA modification and that such molecules may include unmodified nucleotides or internucleoside linkages.
In some or any embodiments, the inhibitory nucleic acid comprises at least one nucleotide and/or nucleoside modification (e.g., modified bases or with modified sugar moieties), modified internucleoside linkages, and/or combinations thereof. Thus, inhibitory nucleic acids can comprise natural as well as modified nucleosides and linkages. Examples of such chimeric inhibitory nucleic acids, including hybrids or gapmers, are described below.
In some embodiments, the inhibitory nucleic acid comprises one or more modifications comprising: a modified sugar moiety, and/or a modified internucleoside linkage, and/or a modified nucleotide and/or combinations thereof. In some embodiments, the modified internucleoside linkage comprises at least one of: alkylphosphonate, phosphorothioate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethyl ester, or combinations thereof. In some embodiments, the modified sugar moiety comprises a 2′-O-methoxyethyl modified sugar moiety, a 2′-methoxy modified sugar moiety, a 2′-O-alkyl modified sugar moiety, or a bicyclic sugar moiety. Other examples of modifications include locked nucleic acid (LNA), peptide nucleic acid (PNA), arabinonucleic acid (ANA), optionally with 2′-F modification, 2′-fluoro-D-Arabinonucleic acid (FANA), phosphorodiamidate morpholino oligomer (PMO), ethylene-bridged nucleic acid (ENA), optionally with 2′-0,4′-C-ethylene bridge, and bicyclic nucleic acid (BNA). Yet other examples are described below and/or are known in the art.
In some embodiments, the inhibitory nucleic acid is 5-40 bases in length (e.g., 12-30, 12-28, 12-25). The inhibitory nucleic acid may also be 10-50, or 5-50 bases length. For example, the inhibitory nucleic acid may be one of any of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 bases in length. In some embodiments, the inhibitory nucleic acid is double stranded and comprises an overhang (optionally 2-6 bases in length) at one or both termini. In other embodiments, the inhibitory nucleic acid is double stranded and blunt-ended. In some embodiments, the inhibitory nucleic acid comprises or consists of a sequence of bases at least 80% or 90% complementary to, e.g., at least 5, 10, 15, 20, 25 or 30 bases of, or up to 30 or 40 bases of, the target RNA, or comprises a sequence of bases with up to 3 mismatches (e.g., up to 1, or up to 2 mismatches) over 10, 15, 20, 25 or 30 bases of the target RNA.
Thus, the inhibitory nucleic acid can comprise or consist of a sequence of bases at least 80% complementary to at least 10 contiguous bases of the target RNA, or at least 80% complementary to at least 15, or 15-30, or 15-40 contiguous bases of the target RNA, or at least 80% complementary to at least 20, or 20-30, or 20-40 contiguous bases of the target RNA, or at least 80% complementary to at least 25, or 25-30, or 25-40 contiguous bases of the target RNA, or at least 80% complementary to at least 30, or 30-40 contiguous bases of the target RNA, or at least 80% complementary to at least 40 contiguous bases of the target RNA. Moreover, the inhibitory nucleic acid can comprise or consist of a sequence of bases at least 90% complementary to at least 10 contiguous bases of the target RNA, or at least 90% complementary to at least 15, or 15-30, or 15-40 contiguous bases of the target RNA, or at least 90% complementary to at least 20, or 20-30, or 20-40 contiguous bases of the target RNA, or at least 90% complementary to at least 25, or 25-30, or 25-40 contiguous bases of the target RNA, or at least 90% complementary to at least 30, or 30-40 contiguous bases of the target RNA, or at least 90% complementary to at least 40 contiguous bases of the target RNA. Similarly, the inhibitory nucleic acid can comprise or consist of a sequence of bases fully complementary to at least 5, 10, or 15 contiguous bases of the target RNA.
Complementarity can also be referenced in terms of the number of mismatches in complementary base pairing, as noted above. Thus, the inhibitory nucleic acid can comprise or consist of a sequence of bases with up to 3 mismatches over 10 contiguous bases of the target RNA, or up to 3 mismatches over 15 contiguous bases of the target RNA, or up to 3 mismatches over 20 contiguous bases of the target RNA, or up to 3 mismatches over 25 contiguous bases of the target RNA, or up to 3 mismatches over 30 contiguous bases of the target RNA. Similarly, the inhibitory nucleic acid can comprise or consist of a sequence of bases with up to 2 mismatches over 10 contiguous bases of the target RNA, or up to 2 mismatches over 15 contiguous bases of the target RNA, or up to 2 mismatches over 20 contiguous bases of the target RNA, or up to 2 mismatches over 25 contiguous bases of the target RNA, or up to 2 mismatches over 30 contiguous bases of the target RNA. Similarly, the the inhibitory nucleic acid can comprise or consist of a sequence of bases with one mismatch over 10, 15, 20, 25 or 30 contiguous bases of the target RNA.
As such, in some embodiments the inhibitory nucleic acid comprises or consists of a sequence of bases about 5 to 40, or 8 to 40, or 10 to 50, or 5 to 50 bases in length, comprising a base sequence at least 80% complementary to (optionally one of at least 90%, 95%, 96%, 97%, 98%, 99% or 100% complementary to) a contiguous sequence of at least 5 to 40 bases, or 8 to 40, or 10 to 50, or 5 to 50 bases (optionally one of at least 10, 15, 20, 25 or 30 bases, or one of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 bases) of the target RNA. Thus, in some embodiments the inhibitory nucleic acid may comprise or consist of a sequence of at least 5 to 40, or 8 to 40, or 5 to 50, or 10 to 50, bases (optionally one of at least 10, 15, 20, 25 or 30 bases, or one of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 bases) having at least 80% identity to (optionally one of at least 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to) a contiguous sequence of bases of the same length of an antisense nucleic acid that is completely complementary in sequence to the target RNA. In some embodiments the sequence of the inhibitory nucleic acid may contain 1, 2 or 3 mismatches in complementary base pairing compared to the target ncRNA sequence, over 10, 15, 20, 25 or 30 bases (optionally one of 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 bases) of the target RNA.
In some or any embodiments, the inhibitory nucleic acid is 5 to 40, or 8 to 40, or 10 to 50 bases in length (e.g., 12-30, 12-28, 12-25, 5-25, or 10-25, bases in length), and comprises a sequence of bases with up to 3 mismatches in complementary base pairing over 15 bases of, or up to 2 mismatches over 10 bases.
In some embodiments, gene expression is modulated in a cell. In some embodiments, the cell is a cancer cell, e.g., a tumor cell, in vitro or in vivo, e.g., in a subject. In other embodiments, the cell is a stem cell that is contacted with the inhibitory nucleic acid, PRC1-binding ncRNA, or fragment thereof, ex vivo, for example to enhance pluripotency, enhance differentiation, or induce the stem cell to differentiate to a particular cell type, e.g. nerve, neuron, dopaminergic neuron, muscle, skin, heart, kidney, liver, lung, neuroendocrine, retinal, retinal pigment epithelium, pancreatic alpha or beta cells, hematopoietic, chondrocyte, bone cells and/or blood cells (e.g., T-cells, B-cells, macrophages, erythrocytes, platelets, and the like).
In an additional aspect, the invention provides methods for enhancing pluripotency of a stem cell. The methods include contacting the cell with an inhibitory nucleic acid that specifically binds, or is complementary, to a nucleic acid sequence that is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous to a PRC1-binding fragment thereof, as referred to in Tables 1-3. PRC1-binding fragments of murine or orthologous RNAs, including human RNAs, are contemplated in the aforementioned method.
In a further aspect, the invention features methods for enhancing differentiation of a stem cell, the method comprising contacting the cell with an inhibitory nucleic acid that specifically binds, or is complementary, to a PRC1-binding RNA sequence as set forth in SEQ ID NOS. 17416 to 36368 [mouse Peaks] or 1 to 5893 [human Peaks] or 5894 to 17416 [human Peaks identified by LiftOver].
In some embodiments, the stem cell is an embryonic stem cell. In some embodiments, the stem cell is an iPS cell or an adult stem cell.
In an additional aspect, the invention provides sterile compositions including an inhibitory nucleic acid that specifically binds to or is at least 90% complementary to (e.g., at least 5, 10, 15, 20, 25 or 30 bases of, or up to 30 or 40 bases of) a sequence listed in any of Tables 1-3, or any one of SEQ ID NOs: 17416 to 36368 [mouse Peaks] or 1 to 5893 [human Peaks] or 5894 to 17416 [human Peaks identified by LiftOver], or a related naturally occurring RNA at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to at least 15 (e.g., at least 20, 21, 25, 30, 100) nucleobases of an ncRNA of any of Tables 1-3 or any one of SEQ ID NOs: 17416 to 36368 [mouse Peaks] or 1 to 5893 [human Peaks] or 5894 to 17416 [human Peaks identified by LiftOver], for parenteral administration. In some embodiments, the inhibitory nucleic acid is selected from the group consisting of antisense oligonucleotides, ribozymes, external guide sequence (EGS) oligonucleotides, siRNA compounds, micro RNAs (miRNAs); small, temporal RNAs (stRNA), and single- or double-stranded RNA interference (RNAi) compounds. In some embodiments, the RNAi compound is selected from the group consisting of short interfering RNA (siRNA); or a short, hairpin RNA (shRNA); small RNA-induced gene activation (RNAa); and small activating RNAs (saRNAs).
In some embodiments, the antisense oligonucleotide is selected from the group consisting of antisense RNAs, antisense DNAs, chimeric antisense oligonucleotides, and antisense oligonucleotides.
In some embodiments, the inhibitory nucleic acid comprises one or more modifications comprising: a modified sugar moiety, a modified internucleoside linkage, a modified nucleotide and/or combinations thereof. In some embodiments, the modified internucleoside linkage comprises at least one of: alkylphosphonate, phosphorothioate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethyl ester, or combinations thereof. In some embodiments, the modified sugar moiety comprises a 2′-O-methoxyethyl modified sugar moiety, a 2′-methoxy modified sugar moiety, a 2′-O-alkyl modified sugar moiety, or a bicyclic sugar moiety. Other examples of modifications include locked nucleic acid (LNA), peptide nucleic acid (PNA), arabinonucleic acid (ANA), optionally with 2′-F modification, 2′-fluoro-D-Arabinonucleic acid (FANA), phosphorodiamidate morpholino oligomer (PMO), ethylene-bridged nucleic acid (ENA), optionally with 2′-0,4′-C-ethylene bridge, and bicyclic nucleic acid (BNA). Yet other examples are described below and/or are known in the art.
PRC1-binding fragments of any of the RNA sequences set forth in the sequence listing as summarized below are contemplated. In some aspects, the fragments may recruit PRC1 and enhance PRC1 activity, thereby repressing gene expression, while in other instances the fragments may interfere with PRC1 activity by masking the ncRNA-binding sites on PRC1. In particular, the invention features uses of fragments of the RNA below to modulate expression of any of the genes set forth in Tables 1-3, for use in treating a disease, disorder, condition or association (whether in the “opposite strand” column or the “same strand” column).
Moreover, inhibitory nucleic acids that specifically bind to any of the RNA peaks set forth in the sequence listing as summarized below, any one of SEQ ID NOs: 1 to 5893, 5894 to 17415, or 17416 to 36368, are also contemplated. In particular, the invention features uses of these inhibitory nucleic acids to upregulate expression of any of the genes set forth in Tables 1-3, for use in treating a disease, disorder, condition or association known in the art (whether in the “opposite strand” column or the “same strand”); upregulations of a set of genes grouped together in any one of the categories is contemplated. In some embodiments it is contemplated that expression may be increased by at least about 15-fold, 20-fold, 30-fold, 40-fold, 50-fold or 100-fold, or any range between any of the foregoing numbers. In other experiments, increased mRNA expression has been shown to correlate to increased protein expression.
Thus, in various aspects, the invention features inhibitory nucleic acids that specifically bind to any of the RNA sequences of any of Tables 1-3, for use in modulating expression of a group of reference genes that fall within any one or more of the categories set forth in the tables, and for treating corresponding diseases, disorders or conditions.
In another aspect, the invention also features inhibitory nucleic acids that specifically bind, or are complementary, to any of the RNA sequences of SEQ ID NOS: 17416 to 36368 [mouse Peaks] or 1 to 5893 [human Peaks] or 5894 to 17416 [human Peaks identified by LiftOver], whether in the “opposite strand” column or the “same strand” column of Tables 1-3. In some embodiments, the inhibitory nucleic acid is provided for use in a method of modulating expression of a gene targeted by the PRC1-binding RNA (e.g., an intersecting or nearby gene, as set forth in any of Tables 1-4 below). Such methods may be carried out in vitro, ex vivo, or in vivo. In some embodiments, the inhibitory nucleic acid is provided for use in methods of treating disease, e.g. as described below. The treatments may involve modulating expression (either up or down) of a gene targeted by the PRC1-binding RNA, preferably upregulating gene expression. In some embodiments, the inhibitory nucleic acid is formulated as a sterile composition for parenteral administration. Thus, in one aspect the invention describes a group of inhibitory nucleic acids that specifically bind, or are complementary to, a group of RNA sequences, i.e., Peaks, in any one of Tables 1, 2, or 3. In particular, the invention features uses of such inhibitory nucleic acids to upregulate expression of any of the reference genes set forth in Tables 1-3, for use in treating a disease, disorder, or condition.
It is understood that inhibitory nucleic acids of the invention may be complementary to, or specifically bind to, Peaks, or regions adjacent to (within 100, 200, 300, 400, or 500 nts of) Peaks, as shown in Tables 1-3.
Also provided herein are methods for treating a subject with MECP2 Duplication Syndrome. The methods include administering a therapeutically effective amount of an inhibitory nucleic acid targeting a PRC1-binding region on Mecp2 RNA, e.g., an inhibitory nucleic acid targeting a sequence within the 3′UTR of Mecp2. In some embodiments, inhibitory nucleic acid comprises any of SEQ ID NOs:36399 to 36404.
Further provided herein are methods for treating a subject with systemic lupus erythematosus. The methods include administering a therapeutically effective amount of an inhibitory nucleic acid targeting a PRC1-binding region on IRAK1 RNA, e.g., an inhibitory nucleci acid targeting a sequence within the 3′UTR of IRAK1.
In some embodiments, the inhibitory nucleic acid comprises any of SEQ ID NOs:36396 to 36398.
In some embodiments, the inhibitory nucleic acid comprises at least one locked nucleotide.
Also provided herein are inhibitory nucleic acids targeting a PRC1-binding region on Mecp2 RNA, preferably wherein the PRC1 binding region comprises SEQ ID NO:5876 or 5877, and/or preferably an inhibitory nucleic acid targeting a sequence within the 3′UTR of Mecp2, for use in treating a subject with MECP2 Duplication Syndrome, e.g., comprising any of SEQ ID NOs:36399 to 36404.
In addition, provided herein are inhibitory nucleic acids targeting a PRC1-binding region on IRAK1 RNA, preferably wherein the PRC1 binding region comprises SEQ ID NO:5874 or 5875, and/or preferably an inhibitory nucleic acid targeting a sequence within the 3′UTR of IRAK1, for use in treating a subject with systemic lupus erythematosus, e.g., an inhibitory nucleic acid comprising any of SEQ ID NOs:36396 to 36398.
In some or any embodiments, the inhibitory nucleic acids are, e.g., about 5 to 40, about 8 to 40, or 10 to 50 bases, or 5 to 50 bases in length. In some embodiments, the inhibitory nucleic acid comprises or consists of a sequence of bases at least 80% or 90% complementary to, e.g., at least 5, 10, 15, 20, 25 or 30 bases of, or up to 30 or 40 bases of, the target RNA (e.g., any one of SEQ ID NOs: 1 to 36,368), or comprises a sequence of bases with up to 3 mismatches (e.g., up to 1, or up to 2 mismatches) over 10, 15, 20, 25 or 30 bases of the target RNA.
Thus, as noted above, the inhibitory nucleic acid can comprise or consist of a sequence of bases at least 80% complementary to at least 10, or 10-30 or 10-40 contiguous bases of the target RNA, or at least 80% complementary to at least 15, or 15-30, or 15-40 contiguous bases of the target RNA, or at least 80% complementary to at least 20, or 20-30, or 20-40 contiguous bases of the target RNA, or at least 80% complementary to at least 25, or 25-30, or 25-40 contiguous bases of the target RNA, or at least 80% complementary to at least 30, or 30-40 contiguous bases of the target RNA, or at least 80% complementary to at least 40 contiguous bases of the target RNA. Moreover, the inhibitory nucleic acid can comprise or consist of a sequence of bases at least 90% complementary to at least 5, or 5-30 or 5-40 or 8-40 contiguous bases of the target RNA, or at least 90% complementary to at least 10, or 10-30, or 10-40 contiguous bases of the target RNA, or at least 90% complementary to at least 15, or 15-30, or 15-40 contiguous bases of the target RNA, or at least 90% complementary to at least 20, or 20-30, or 20-40 contiguous bases of the target RNA, or at least 90% complementary to at least 25, or 25-30, or 25-40 contiguous bases of the target RNA, or at least 90% complementary to at least 30, or 30-40 contiguous bases of the target RNA, or at least 90% complementary to at least 40 contiguous bases of the target RNA. Similarly, the inhibitory nucleic acid can comprise or consist of a sequence of bases fully complementary to at least 5, 10, or 15 contiguous bases of the target RNA. It is understood that some additional non-complementary bases may be included. It is understood that inhibitory nucleic acids that comprise such sequences of bases as described may also comprise other non-complementary bases. For example, an inhibitory nucleic acid can be 20 bases in total length but comprise a 15 base portion that is fully complementary to 15 bases of the target RNA. Similarly, an inhibitory nucleic acid can be 20 bases in total length but comprise a 15 base portion that is at least 80% complementary to 15 bases of the target RNA.
Complementarity can also be referenced in terms of the number of mismatches in complementary base pairing, as noted above. Thus, the inhibitory nucleic acid can comprise or consist of a sequence of bases with up to 3 mismatches over 10 contiguous bases of the target RNA, or up to 3 mismatches over 15 contiguous bases of the target RNA, or up to 3 mismatches over 20 contiguous bases of the target RNA, or up to 3 mismatches over 25 contiguous bases of the target RNA, or up to 3 mismatches over 30 contiguous bases of the target RNA. Similarly, the inhibitory nucleic acid can comprise or consist of a sequence of bases with up to 2 mismatches over 10 contiguous bases of the target RNA, or up to 2 mismatches over 15 contiguous bases of the target RNA, or up to 2 mismatches over 20 contiguous bases of the target RNA, or up to 2 mismatches over 25 contiguous bases of the target RNA, or up to 2 mismatches over 30 contiguous bases of the target RNA. Similarly, the the inhibitory nucleic acid can comprise or consist of a sequence of bases with one mismatch over 10, 15, 20, 25 or 30 contiguous bases of the target RNA.
In some or any of the embodiments of inhibitory nucleic acids described herein (e.g. in the summary, detailed description, or examples of embodiments) or the processes for designing or synthesizing them, the inhibitory nucleic acids may optionally exclude (a) any LNA that disrupts binding of PRC2 to an RNA, e.g., as describe in WO 2012/087983 or WO 2012/065143; (b) any one or more of the specific inhibitory nucleic acids made or actually disclosed (i.e. specific chemistry, single or double-stranded, specific modifications, and specific base sequence), set forth in WO 2012/065143 or WO 2012/087983; and/or the general base sequence of any one or more of the inhibitory nucleic acids of (b); and/or (c) the group of inhibitory nucleic acids that specifically bind or are complementary to the same specific portion of RNA (a stretch of contiguous bases) as any one or more of the inhibitory nucleic acids of (a); as disclosed in any one or more of the following publications: as targeting ANRIL RNA (as described in Yap et al., Mol Cell. 2010 Jun. 11; 38(5):662-74) HOTAIR RNA (Rinn et al., 2007), Tsix, RepA, or Xist RNAs ((Zhao et al., 2008) [SEQ ID NOs: 936166-936170 of WO 2012/087983], or (Sarma et al., 2010) [SEQ ID NOs: 936177-936186 of WO 2012/087983] or (Zhao et al., 2010) [SEQ ID NOs: 936187-936188 of WO 2012/087983] or (Prasnath et al., 2005) [SEQ ID NOs: 936173-936176 of WO 2012/087983] or (Shamovsky et al., 2006) [SEQ ID NO: 936172 of WO 2012/087983] or (Mariner et al., 2008) [SEQ ID NO: 936171 of WO 2012/087983] or (Sunwoo et al., 2008) or (Bernard et al., 2010) [SEQ ID NO: 936189 of WO 2012/087983]; or as targeting short RNAs of 50-200 nt that are identified as candidate PRC2 regulators (Kanhere et al., 2010); or (Kuwabara et al., US 2005/0226848) [SEQ ID NOs: 936190-936191 of WO 2012/087983] or (Li et al., US 2010/0210707) [SEQ ID NOs: 936192-936227 of WO 2012/087983] or (Corey et al., U.S. Pat. No. 7,709,456) [SEQ ID NOs: 936228-936245] or (Mattick et al., WO 2009/124341), or (Corey et al., US 2010/0273863) [SEQ ID NOs: 936246-936265 of WO 2012/087983], or (Wahlstedt et al., US 2009/0258925) [SEQ ID NOs: 935060-935126 of WO 2012/087983], or BACE: US 2009/0258925 [SEQ ID NOs: 935060-935126 of WO 2012/087983]; ApoA1: US 2010/0105760/EP235283 [SEQ ID NOs: 935127-935299 of WO 2012/087983], P73, p53, PTEN, WO 2010/065787 A2/EP2370582 [SEQ ID NOs: 935300-935345 of WO 2012/087983]; SIRT1: WO 2010/065662 A2/EP09831068 [SEQ ID NOs: 935346-935392 of WO 2012/087983]; VEGF: WO 2010/065671 A2/EP2370581 [SEQ ID NOs: 935393-935403 of WO 2012/087983]; EPO: WO 2010/065792 A2/EP09831152 [SEQ ID NOs: 935404-935412 of WO 2012/087983]; BDNF: WO2010/093904 [SEQ ID NOs: 935413-935423 of WO 2012/087983], DLK1: WO 2010/107740 [SEQ ID NOs: 935424-935430 of WO 2012/087983]; NRF2/NFE2L2: WO 2010/107733 [SEQ ID NOs: 935431-935438 of WO 2012/087983]; GDNF: WO 2010/093906 [SEQ ID NOs: 935439-935476 of WO 2012/087983]; SOX2, KLF4, Oct3A/B, “reprogramming factors: WO 2010/135329 [SEQ ID NOs: 935477-935493 of WO 2012/087983]; Dystrophin: WO 2010/129861 [SEQ ID NOs: 935494-935525 of WO 2012/087983]; ABCA1, LCAT, LRP1, ApoE, LDLR, ApoA1: WO 2010/129799 [SEQ ID NOs: 935526-935804 of WO 2012/087983]; HgF: WO 2010/127195 [SEQ ID NOs: 935805-935809 of WO 2012/087983]; TTP/Zfp36: WO 2010/129746[SEQ ID NOs: 935810-935824 of WO 2012/087983]; TFE3, IRS2: WO 2010/135695 [SEQ ID NOs: 935825-935839 of WO 2012/087983]; RIG1, MDAS, IFNA1: WO 2010/138806 [SEQ ID NOs: 935840-935878 of WO 2012/087983]; PON1: WO 2010/148065 [SEQ ID NOs: 935879-935885 of WO 2012/087983]; Collagen: WO/2010/148050 [SEQ ID NOs: 935886-935918 of WO 2012/087983]; DyrklA, Dscrl, “Down Syndrome Gene”: WO/2010/151674 [SEQ ID NOs: 935919-935942 of WO 2012/087983]; TNFR2: WO/2010/151671 [SEQ ID NOs: 935943-935951 of WO 2012/087983]; Insulin: WO/2011/017516 [SEQ ID NOs: 935952-935963 of WO 2012/087983]; ADIPOQ: WO/2011/019815 [SEQ ID NOs: 935964-935992 of WO 2012/087983]; CHIP: WO/2011/022606 [SEQ ID NOs: 935993-936004 of WO 2012/087983]; ABCB1: WO/2011/025862 [SEQ ID NOs: 936005-936014 of WO 2012/087983]; NEUROD1, EUROD1, HNF4A, MAFA, PDX, KX6, “Pancreatic development gene”: WO/2011/085066 [SEQ ID NOs: 936015-936054 of WO 2012/087983]; MBTPS1: WO/2011/084455 [SEQ ID NOs: 936055-936059 of WO 2012/087983]; SHBG: WO/2011/085347 [SEQ ID NOs: 936060-936075 of WO 2012/087983]; IRF8: WO/2011/082409 [SEQ ID NOs: 936076-936080 of WO 2012/087983]; UCP2: WO/2011/079263 [SEQ ID NOs: 936081-936093 of WO 2012/087983]; HGF: WO/2011/079261 [SEQ ID NOs: 936094-936104 of WO 2012/087983]; GH: WO/2011/038205 [SEQ ID NOs: 936105-936110 of WO 2012/087983]; IQGAP: WO/2011/031482 [SEQ ID NOs: 936111-936116 of WO 2012/087983]; NRF1: WO/2011/090740 [SEQ ID NOs: 936117-936123 of WO 2012/087983]; P63: WO/2011/090741 [SEQ ID NOs: 936124-936128 of WO 2012/087983]; RNAseHl: WO/2011/091390 [SEQ ID NOs: 936129-936140 of WO 2012/087983]; ALOX12B: WO/2011/097582 [SEQ ID NOs: 936141-936146 of WO 2012/087983]; PYCR1: WO/2011/103528 [SEQ ID NOs: 936147-936151 of WO 2012/087983]; CSF3: WO/2011/123745 [SEQ ID NOs: 936152-936157 of WO 2012/087983]; FGF21: WO/2011/127337 [SEQ ID NOs: 936158-936165 of WO 2012/087983]; SIRTUIN (SIRT): WO2011/139387 [SEQ ID NOs: 936266-936369 and 936408-936425 of WO 2012/087983]; PAR4: WO2011/143640 [SEQ ID NOs: 936370-936376 and 936426 of WO 2012/087983]; LHX2: WO2011/146675 [SEQ ID NOs: 936377 936388 and 936427-936429 of WO 2012/087983]; BCL2L11: WO2011/146674 [SEQ ID NO: 936389-936398 and 936430-936431 of WO 2012/087983]; MSRA: WO2011/150007 [SEQ ID NOs: 936399-936405 and 936432 of WO 2012/087983]; ATOH1: WO2011/150005 [SEQ ID NOs: 936406-936407 and 936433 of WO 2012/087983] of which each of the foregoing is incorporated by reference in its entirety herein. In some or any of the embodiments, optionally excluded from the invention are of inhibitory nucleic acids that specifically bind to, or are complementary to, any one or more of the following regions: Nucleotides 1-932 of SEQ ID NO: 935128 of WO 2012/087983; Nucleotides 1-1675 of SEQ ID NO: 935306 of WO 2012/087983; Nucleotides 1-518 of SEQ ID NO: 935307 of WO 2012/087983; Nucleotides 1-759 of SEQ ID NO: 935308 of WO 2012/087983; Nucleotides 1-25892 of SEQ ID NO: 935309 of WO 2012/087983; Nucleotides 1-279 of SEQ ID NO: 935310 of WO 2012/087983; Nucleotides 1-1982 of SEQ ID NO: 935311 of WO 2012/087983; Nucleotides 1-789 of SEQ ID NO: 935312 of WO 2012/087983; Nucleotides 1-467 of SEQ ID NO: 935313 of WO 2012/087983; Nucleotides 1-1028 of SEQ ID NO: 935347 of WO 2012/087983; Nucleotides 1-429 of SEQ ID NO: 935348 of WO 2012/087983; Nucleotides 1-156 of SEQ ID NO: 935349 of WO 2012/087983; Nucleotides 1-593 of SEQ ID NO:935350 of WO 2012/087983; Nucleotides 1-643 of SEQ ID NO: 935395 of WO 2012/087983; Nucleotides 1-513 of SEQ ID NO: 935396 of WO 2012/087983; Nucleotides 1-156 of SEQ ID NO: 935406 of WO 2012/087983; Nucleotides 1-3175 of SEQ ID NO: 935414 of WO 2012/087983; Nucleotides 1-1347 of SEQ ID NO: 935426 of WO 2012/087983; Nucleotides 1-5808 of SEQ ID NO: 935433 of WO 2012/087983; Nucleotides 1-237 of SEQ ID NO: 935440 of WO 2012/087983; Nucleotides 1-1246 of SEQ ID NO: 935441 of WO 2012/087983; Nucleotides 1-684 of SEQ ID NO: 935442 of WO 2012/087983; Nucleotides 1-400 of SEQ ID NO: 935473 of WO 2012/087983; Nucleotides 1-619 of SEQ ID NO: 935474 of WO 2012/087983; Nucleotides 1-813 of SEQ ID NO: 935475 of WO 2012/087983; Nucleotides 1-993 of SEQ ID NO: 935480 of WO 2012/087983; Nucleotides 1-401 of SEQ ID NO: 935480 of WO 2012/087983; Nucleotides 1-493 of SEQ ID NO: 935481 of WO 2012/087983; Nucleotides 1-418 of SEQ ID NO: 935482 of WO 2012/087983; Nucleotides 1-378 of SEQ ID NO: 935496 of WO 2012/087983; Nucleotides 1-294 of SEQ ID NO: 935497 of WO 2012/087983; Nucleotides 1-686 of SEQ ID NO: 935498 of WO 2012/087983; Nucleotides 1-480 of SEQ ID NO: 935499 of WO 2012/087983; Nucleotides 1-501 of SEQ ID NO: 935500 of WO 2012/087983; Nucleotides 1-1299 of SEQ ID NO: 935533 of WO 2012/087983; Nucleotides 1-918 of SEQ ID NO: 935534 of WO 2012/087983; Nucleotides 1-1550 of SEQ ID NO: 935535 of WO 2012/087983; Nucleotides 1-329 of SEQ ID NO: 935536 of WO 2012/087983; Nucleotides 1-1826 of SEQ ID NO: 935537 of WO 2012/087983; Nucleotides 1-536 of SEQ ID NO: 935538 of WO 2012/087983; Nucleotides 1-551 of SEQ ID NO: 935539 of WO 2012/087983; Nucleotides 1-672 of SEQ ID NO: 935540 of WO 2012/087983; Nucleotides 1-616 of SEQ ID NO: 935541 of WO 2012/087983; Nucleotides 1-471 of SEQ ID NO: 935542 of WO 2012/087983; Nucleotides 1-707 of SEQ ID NO: 935543 of WO 2012/087983; Nucleotides 1-741 of SEQ ID NO: 935544 of WO 2012/087983; Nucleotides 1-346 of SEQ ID NO: 935545 of WO 2012/087983; Nucleotides 1-867 of SEQ ID NO: 935546 of WO 2012/087983; Nucleotides 1-563 of SEQ ID NO: 935547 of WO 2012/087983; Nucleotides 1-970 of SEQ ID NO: 935812 of WO 2012/087983; Nucleotides 1-1117 of SEQ ID NO: 935913 of WO 2012/087983; Nucleotides 1-297 of SEQ ID NO: 935814 of WO 2012/087983; Nucleotides 1-497 of SEQ ID NO: 935827 of WO 2012/087983; Nucleotides 1-1267 of SEQ ID NO: 935843 of WO 2012/087983; Nucleotides 1-586 of SEQ ID NO: 935844 of WO 2012/087983; Nucleotides 1-741 of SEQ ID NO: 935845 of WO 2012/087983; Nucleotides 1-251 of SEQ ID NO: 935846 of WO 2012/087983; Nucleotides 1-681 of SEQ ID NO: 935847 of WO 2012/087983; Nucleotides 1-580 of SEQ ID NO: 935848 of WO 2012/087983; Nucleotides 1-534 of SEQ ID NO: 935880 of WO 2012/087983; Nucleotides 1-387 of SEQ ID NO: 935889 of WO 2012/087983; Nucleotides 1-561 of SEQ ID NO: 935890 of WO 2012/087983; Nucleotides 1-335 of SEQ ID NO: 935891 of WO 2012/087983; Nucleotides 1-613 of SEQ ID NO: 935892 of WO 2012/087983; Nucleotides 1-177 of SEQ ID NO: 935893 of WO 2012/087983; Nucleotides 1-285 of SEQ ID NO: 935894 of WO 2012/087983; Nucleotides 1-3814 of SEQ ID NO: 935921 of WO 2012/087983; Nucleotides 1-633 of SEQ ID NO: 935922 of WO 2012/087983; Nucleotides 1-497 of SEQ ID NO: 935923 Nucleotides 1-545 of SEQ ID NO: 935924 of WO 2012/087983; Nucleotides 1-413 of SEQ ID NO: 935950 of WO 2012/087983; Nucleotides 1-413 of SEQ ID NO: 935951 of WO 2012/087983; Nucleotides 1-334 of SEQ ID NO: 935962 of WO 2012/087983; Nucleotides 1-582 of SEQ ID NO: 935963 of WO 2012/087983; Nucleotides 1-416 of SEQ ID NO: 935964 of WO 2012/087983; Nucleotides 1-3591 of SEQ ID NO: 935990 of WO 2012/087983; Nucleotides 1-875 of SEQ ID NO: 935991 of WO 2012/087983; Nucleotides 1-194 of SEQ ID NO: 935992 of WO 2012/087983; Nucleotides 1-2074 of SEQ ID NO: 936003 of WO 2012/087983; Nucleotides 1-1237 of SEQ ID NO: 936004 of WO 2012/087983; Nucleotides 1-4050 of SEQ ID NO: 936013 of WO 2012/087983; Nucleotides 1-1334 of SEQ ID NO: 936014 of WO 2012/087983; Nucleotides 1-1235 of SEQ ID NO: 936048 of WO 2012/087983; Nucleotides 1-17,964 of SEQ ID NO: 936049 of WO 2012/087983; Nucleotides 1-50,003 of SEQ ID NO: 936050 of WO 2012/087983; Nucleotides 1-486 of SEQ ID NO: 936051 of WO 2012/087983; Nucleotides 1-494 of SEQ ID NO: 936052 of WO 2012/087983; Nucleotides 1-1992 of SEQ ID NO: 936053 of WO 2012/087983; Nucleotides 1-1767 of SEQ ID NO: 936054 of WO 2012/087983; Nucleotides 1-1240 of SEQ ID NO: 936059 of WO 2012/087983; Nucleotides 1-3016 of SEQ ID NO: 936074 of WO 2012/087983; Nucleotides 1-1609 of SEQ ID NO: 936075 of WO 2012/087983; Nucleotides 1-312 of SEQ ID NO: 936080 of WO 2012/087983; Nucleotides 1-243 of SEQ ID NO: 936092 of WO 2012/087983; Nucleotides 1-802 of SEQ ID NO: 936093 of WO 2012/087983; Nucleotides 1-514 of SEQ ID NO: 936102 of WO 2012/087983; Nucleotides 1-936 of SEQ ID NO: 936103 of WO 2012/087983; Nucleotides 1-1075 of SEQ ID NO: 936104 of WO 2012/087983; Nucleotides 1-823 of SEQ ID NO: 936110 of WO 2012/087983; Nucleotides 1-979 of SEQ ID NO: 936116 of WO 2012/087983; Nucleotides 1-979 of SEQ ID NO: 936123 of WO 2012/087983; Nucleotides 1-288 of SEQ ID NO: 936128 of WO 2012/087983; Nucleotides 1-437 of SEQ ID NO: 936137 of WO 2012/087983; Nucleotides 1-278 of SEQ ID NO: 936138 of WO 2012/087983; Nucleotides 1-436 of SEQ ID NO: 936139 of WO 2012/087983; Nucleotides 1-1140 of SEQ ID NO: 936140 of WO 2012/087983; Nucleotides 1-2082 of SEQ ID NO: 936146 of WO 2012/087983; Nucleotides 1-380 of SEQ ID NO: 936151 of WO 2012/087983; Nucleotides 1-742 of SEQ ID NO: 936157 of WO 2012/087983; Nucleotides 1-4246 of SEQ ID NO: 936165 of WO 2012/087983; Nucleotides 1-1028 of SEQ ID NO: 936408 of WO 2012/087983; Nucleotides 1-429 of SEQ ID NO: 936409 of WO 2012/087983; Nucleotides 1-508 of SEQ ID NO: 936410 of WO 2012/087983; Nucleotides 1-593 of SEQ ID NO: 936411 of WO 2012/087983; Nucleotides 1-373 of SEQ ID NO: 936412 of WO 2012/087983; Nucleotides 1-1713 of SEQ ID NO: 936413 of WO 2012/087983; Nucleotides 1-660 of SEQ ID NO:936414 of WO 2012/087983; Nucleotides 1-589 of SEQ ID NO: 936415 of WO 2012/087983; Nucleotides 1-726 of SEQ ID NO: 936416 of WO 2012/087983; Nucletides 1-320 of SEQ ID NO: 936417 of WO 2012/087983; Nucletides 1-616 of SEQ ID NO: 936418 of WO 2012/087983; Nucletides 1-492 of SEQ ID NO: 936419 of WO 2012/087983; Nucletides 1-428 of SEQ ID NO: 936420 of WO 2012/087983; Nucletides 1-4041 of SEQ ID NO: 936421 of WO 2012/087983; Nucletides 1-705 of SEQ ID NO: 936422 of WO 2012/087983; Nucletides 1-2714 of SEQ ID NO: 936423 of WO 2012/087983; Nucletides 1-1757 of SEQ ID NO: 936424 of WO 2012/087983; Nucletides 1-3647 of SEQ ID NO: 936425 of WO 2012/087983; Nucleotides 1-354 of SEQ ID NO: 936426 of WO 2012/087983; Nucleotides 1-2145 of SEQ ID NO: 936427, Nucleotides 1-606 of SEQ ID NO: 936428 of WO 2012/087983; Nucleotides 1-480 of SEQ ID NO: 936429 of WO 2012/087983; Nucleotides 1-3026 of SEQ ID NO: 936430 of WO to 2012/087983; Nucleotides 1-1512 of SEQ ID NO: 936431 of WO 2012/087983; Nucleotides 1-3774 of SEQ ID NO: 936432 of WO 2012/087983; Nucleotides 1-589 of SEQ ID NO: 936433.
In some of the embodiments of inhibitory nucleic acids described herein, or processes for designing or synthesizing them, the inhibitory nucleic acids will upregulate gene expression and may specifically bind or specifically hybridize or be complementary to the PRC1-binding RNA that is transcribed from the same strand as a protein coding reference gene. The inhibitory nucleic acid may bind to a region of the PRC1-binding RNA, that originates within or overlaps an intron, exon, intron-exon junction, 5′ UTR, 3′ UTR, a translation initiation region, or a translation termination region of a protein-coding sense-strand of a reference gene (refGene).
In some or any of the embodiments of inhibitory nucleic acids described herein, or processes for designing or syntheisizing them, the inhibitory nucleic acids will upregulate gene expression and may specifically bind or specifically hybridize or be complementary to a PRC1 binding RNA that transcribed from the opposite strand (the antisense-strand) of a protein-coding reference gene.
The inhibitory nucleic acids described herein may be modified, e.g. comprise a modified sugar moiety, a modified internucleoside linkage, a modified nucleotide and/or combinations thereof. In addition, the inhibitory nucleic acids can exhibit one or more of the following properties: do not induce substantial cleavage or degradation of the target RNA; do not cause substantially complete cleavage or degradation of the target RNA; do not activate the RNAse H pathway; do not activate RISC; do not recruit any Argonaute family protein; are not cleaved by Dicer; do not mediate alternative splicing; are not immune stimulatory; are nuclease resistant; have improved cell uptake compared to unmodified oligonucleotides; are not toxic to cells or mammals; may have improved endosomal exit; do interfere with interaction of ncRNA with PRC1, preferably the Ezh2 subunit but optionally the Suz12, Eed, RbAp46/48 subunits or accessory factors such as Jarid2; do decrease histone H3-lysine27 methylation and/or do upregulate gene expression. In some or any of the embodiments of inhibitory nucleic acids described herein, or processes for designing or synthesizing them, the inhibitory nucleic acids may optionally exclude those that bind DNA of a promoter region, as described in Kuwabara et al., US 2005/0226848 or Li et al., US 2010/0210707 or Corey et al., U.S. Pat. No. 7,709,456 or Mattick et al., WO 2009/124341, or those that bind DNA of a 3′ UTR region, as described in Corey et al., US 2010/0273863.
Inhibitory nucleic acids that are designed to interact with RNA to modulate gene expression are a distinct subset of base sequences from those that are designed to bind a DNA target (e.g., are complementary to the underlying genomic DNA sequence from which the RNA is transcribed).
This application incorporates by reference the entire disclosures of U.S. provisional Nos. 61/425,174 filed on Dec. 20, 2010, and 61/512,754 filed on Jul. 28, 2011, and International Patent Application Nos. PCT/US2011/060493, filed Nov. 12, 2011, and PCT/US2011/065939, filed on Dec. 19, 2011.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials are described herein for use in the present invention; other, suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.
Other features and advantages of the invention will be apparent from the following detailed description and figures, and from the claims.

REFERENCE TO SEQUENCE LISTING

This application includes a Sequence Listing in .txt format, filed herewith as SL.txt, a file of 67.2 MB. The entire content of this file is hereby incorporated by reference.

DESCRIPTION OF DRAWINGS

FIGS. 1A-B are schematics of exemplary denaturing CLIP (dCLIP) pull-down methods (1A) and library preparation methods (1B).

FIGS. 2A-C show four test genes for effects of disrupting PRC1-3′UTR interactions. IGV screenshots shown for three Chromobox Homolog 7 (CBX7)-binding RNAs: (2A) Mouse DDB1 and CUL4 Associated Factor 12-Like 1 (Dcaf12L1); (2B) Mouse Calmodulin 2 (Calm2); (2C) Mouse methyl CpG binding protein 2 (Mecp2). For each gene, the RNA-seq profile shows the FPKM expression values of each gene. CLIP-seq profiles are then shown for various biological replicates (e.g., Cbx7 #1, #2, #3). For Dcaf12L1 and Calm2, statistically significant peaks (“Peak”, as called by PeakRanger software) shown as bars under each replicate's track. Two control (tag-only libraries) are shown for each gene. Only the relevant strand is shown (Watson or Crick). Note highly reproducible CLIP profiles and very clean control libraries. ASO LNA mixmers used for knockoff ananlysis are shown as black bars. The mixmers were pooled for the transfections.

FIGS. 3A-C are graphs showing gene upregulation as a result of disrupting PRC1-3′UTR interactions. 16.7 ES cells were nucleofected with pooled mixmer LNAs against Calmodulin 2 (Calm2) (leftmost bars) or DDB1 and CUL4 Associated Factor 12-Like 1 (Dcafl2L1) (middle bars); Dual-specific phosphatase 9 (Dusp9) was used as a negative control (right bars). Cells were harvested after 24 hours and whole cell RNA was used for quantitative gene expression analysis using real-time RT-PCR. Expression of specific transcripts was normalized to beta-actin as a reference gene.

FIGS. 4A-B shows the test gene, Tsix, and results of knocking off PRC1 from Tsix RNA. (4A) The RNA-seq profile shows the Fragments Per Kilobase of transcript per Million mapped reads (FPKM) expression values of each gene. CLIP-seq profiles are then shown for two biological replicates (Cbx7 #1, #2), with corresponding statistically significant peaks (“Peak”, as called by PeakRanger software) shown as bars under each replicate's track. Two control (tag-only libraries) are shown for each gene. Antisense oligonucleotide (ASO) LNA mixmers used for knockoff ananlysis are shown as black bars. The mixmers were pooled for the transfections. Only the Watson strand is shown in the figure. (4B) Tsix RNA is a repressor ofXist expression. Here we hypothesized that Tsix recruits PRC1 to repress Xist expression. The RT-qPCR analysis performed 6 hours after administering Tsix LNAs support this interaction. Xist upregulation was achieved specifically.

Table 1: Human CBX7-RNA binding sites as determined by denaturing CLIP-seq analysis in Human 293 cells. All coordinates in hg19. The columns (c) correspond to: c1, SEQ ID Number. c2, Chromosome number. c3, Read start position. c4, Read end position. c5, chromosome strand that the transcript is made from (+, top or Watson strand; −, bottom or Crick strand of each chromosome). C6, nearest gene name. c7, gene categories as defined in Example 2.
Table 2: Human LiftOver sequences corresponding to CBX7-RNA binding sites as determined by denaturing CLIP-seq analysis in mouse ES cells shown. All coordinates in hg19. CBX7-binding sites derived from CLIP-seq performed in the mouse ES cell line, 16.7, as shown in Table 3, are translated from mouse mm9 to human hg19 coordinates.
Table 3: Mouse CBX7-RNA binding sites as determined by denaturing CLIP-seq analysis in ES cells derived from Mus musculus. All coordinates in mm9. CLIP-seq performed in the mouse ES cell line, EL 16.7. CBX7 binding sites in the RNA are shown.

DETAILED DESCRIPTION

The new ‘denaturing’ CLIP-seq (dCLIP-seq) method, which utilizes a biotin tag to enable purification of RNA-protein complexes under denaturing conditions to increase the specificity of the purification scheme, was used to capture a genome-wide pool of transcripts (>30 nt) that bind with the PRC1 complex via the CBX7 subunit. Transcriptome characterization has identified classes of medically significant targets. Many if not all of the mouse PRC1-transcripts identified herein were shown by LiftOver analysis to have direct counterparts in the human epigenome.
As demonstrated herein, at least a subset of RNAs directly interacts with PRC1 in vivo and, in many cases, the interacting subunit is a CBX protein, e.g., CBX7. In some cases, the interacting subunit is CBX2, 4, 6, or 8. CBX7 is generally expressed earlier in development in less-differentiated cells, while CBX2, 4, 6, 8 are expressed in more differentiated cells and may be more tissue-specific. The CBX family is likely to have highly overlapping RNA interactomes, because the proteins are highly similar to each other and have RNA-binding domains.
The present analysis suggests that both cis and trans mechanisms may be utilized by RNAs in the PRC1 RNA interactome. As shown herein, PRC1 has a number of different cis-regulatory effects. PRC1 binding sites can be classified into several groups, including (i) 3′ untranslated region (3′ UTR), (ii) promoter-associated, (iii) gene body, (iv) antisense, and (v) intergenic. Disrupting the interaction between PRC1 and a binding RNA could lead to either activation or repression. For example, targeting the PRC1 binding sites within the 3′ UTR of Calm2 and Dcaf1211 results in upregulation of these coding genes (FIG. 3 ). Calm2 is a member of the calmodulin gene family, with three distinct calmodulin genes throughout the genome that encode an identical protein. CALM2 is a calcium binding protein that plays a role in signaling pathways, cell cycle progression and proliferation. Mutations are associated with long-QT syndrome (LQTS, life-threatening ventricular arrhythmias) with delayed neurodevelopment and epilepsy. By contrast, targeting various regions within Mecp2 and IRAK1 resulted in gene downregulation (FIGS. 5A-B). The present methods may be especially useful when one aims to titrate down but not eliminate gene expression, such as in the case of MECP2 Duplication Syndrome (a disease in which the MECP2 gene is duplicated and causes an Rett Syndrome-like disorder) or for treating autoimmune or inflammatory diseases, such as systemic lupus erythematosis (SLE), for which IRAK1 (interleukin 1 associated kinase 1) has been implicated.
As used herein, the 3′UTR is the last exon of a protein coding gene that usually includes the last few translated codons and the rest of the untranslated 3′ end of the mRNA encoded by the gene.
The evidence presented herein further demonstrates that RNA cofactors are a general feature of Polycomb regulation and that inhibitory nucleic acids as described herein that target RNAs in the PRC1 RNA interactome can successfully modulate (e.g., upregulate) gene expression, with effects dependent on the target site in the interacting transcript. The effects are presumed to be caused by inhibiting PRC1-RNA interactions. Genes in cis, in either antisense-strand orientation or same strand orientation, and extending 1 kb or more, e.g. 5 or 20 kb, from the location of the PRC1-binding RNA, can be regulated. Because chromatin modifiers such as PRC1 play a central role in maintaining stem cell pluripotency and in cancer, a genome-wide profile of regulatory RNAs will be a valuable resource in the quest to diagnose and treat disease. To downregulate gene expression, targeting RNA-PRC1 interactions by antisense oligonucleotides provides an alternative approach to RNAi methods, when one aims to titrate down but not eliminate gene expression, such as in the case of MECP2 Duplication Syndrome (a disease in which the MECP2 gene is duplicated and causes an Rett Syndrome-like disorder) or for treating autoimmune or inflammatory diseases, such as systemic lupus erythematosis (SLE), for which IRAK1 (interleukin 1 associated kinase 1) has been implicated.
Denaturing CLIP-Seq Methods (dCLIP-Seq)
Described herein are methods for pulling down RNAs that bind to a protein of interest, to produce libraries of those RNAs, and to identify regions of the RNAs to which the proteins bind. These methods were used to identify RNAs that bind the CBX7 portion of the PRC1 complex, but can be used with any proteins known or suspected to bind RNA. In some embodiments, the methods include the steps shown in FIGS. 1A and/or 1B; one of skill in the art will appreciate that other techniques can be substituted for those shown. These include conventional CLIP (see, e.g., Davidovich et al., Mol Cell. 2015 Feb. 5; 57(3):552-8), HITS-CLIP (Darnell, Wiley Interdiscip Rev RNA. 2010 September-October; 1(2): 266-286), PAR-CLIP, iCLIP (huppertz et al., Methods. 2014 February; 65(3): 274-287), and native RIP (Zhao et al., Mol Cell. 2010 Dec. 22; 40(6):939-53).
In preferred embodiments, the methods are practiced using cells, e.g., mammalian cells, that express the bacterial biotin ligase BirA, and an RNA-binding protein of interest, e.g., CBX2, CBX4, CBX6, CBX7, or CBX8, fused to a biotinylation tag sequence. In some embodiments, the BirA and RNA binding protein are on separate vectors, preferably separate vectors with different selectable markers, e.g., different antibiotic resistance genes, or different fluorescent proteins. In some embodiments, the BirA is expressed from a first vector under neomycin resistance, and the protein of interest fused to a biotinylation tag sequence is expressed from a second vector under puromycin resistance. Biotinylation tag sequences are known in the art, see, e.g., Schatz, Biotechnology (N Y). 1993 October; 11(10):1138-43; Tucker and Grisshammer, Biochem J. 1996 Aug. 1; 317 (Pt 3):891-9; and Beckett et al., Protein Sci. 1999 April; 8(4):921-9. An exemplary biotinylation sequence is GLNDIFEAQKIEWHE (SEQ ID NO: 36369); other sequences are known in the art, e.g., GLNDIFEAQKIEWH (SEQ ID NO: 36370); and others as disclosed in Beckett et al., Protein Science 1999, 8:921-929, e.g., in FIG. 5 and Table 2 therein. Sequences for BirA are also known in the art; see, e.g., Howard et al., Gene. 1985; 35(3):321-31. An exemplary protein sequence for BirA is as follows:

	(SEQ ID NO: 36371)
	10 20 30 40
	MKDNTVPLKL IALLANGEFH SGEQLGETLG MSRAAINKHI

	50 60 70 80
	QTLRDWGVDV FTVPGKGYSL PEPIQLLNAK QILGQLDGGS

	90 100 110 120
	VAVLPVIDST NQYLLDRIGE LKSGDACIAE YQQAGRGRRG

	130 140 150 160
	RKWFSPFGAN LYLSMFWRLE QGPAAAIGLS LVIGIVMAEV

	170 180 190 200
	LRKLGADKVR VKWPNDLYLQ DRKLAGILVE LTGKTGDAAQ

	210 220 230 240
	IVIGAGINMA MRRVEESVVN QGWITLQEAG INLDRNTLAA

	250 260 270 280
	MLIRELRAAL ELFEQEGLAP YLSRWEKLDN FINRPVKLII

	290 300 310 320
	GDKEIFGISR GIDKQGALLL EQDGIIKPWM GGEISLRSAE

	K

Additional exemplary sequences include those at GenBank Acc. No. NP_418404.1 and YP_491483.1; exemplary coding sequences can be found at NC_000913.3 and NC_007779.1.

Cells are crosslinked by exposure to ultraviolet (UV) light (e.g., preferably 254 nm, but a range of 200 nm to 400 nm may be possible), cellular lysates are prepared, then DNAsed to solubilize the chromatin, and protein-RNA complexes are pulled down using streptavidin beads. Importantly, the samples are then washed, preferably with a high stringency wash, e.g., using 8 M urea (range: 5-10 M, 6-10M, 7-10M, 7-9M, or 7.5-8.5M)+0.1% SDS (range: 0.0-2.0%). Other detergents may be used as substitutes for SDS, including Triton X-100 and NP40. Samples can then be further washed, e.g., in PBS+2% SDS and further in high salt buffer (e.g., PBS+750 mM NaCl+1% NP40+0.5% NaDeoxycholate+0.1% SDS; variations on salt/detergent conditions are possible). Under such suitable stringent conditions, most proteins are denatured, resulting in the loss of the nonspecific RNA-protein interactions. Only the extremely high-affinity biotin-avidin interaction survives. Thus, these steps can be used to effectively remove the vast majority of background RNA, resulting in extremely clean “peaks” of binding. The samples are then treated with DNAse to remove contaminating DNA. The RNA is phosphorylated using P32-ATP and run on SDS-PAGE and transferred onto membrane. Bands corresponding to the protein-RNA complex are then excised and eluted for cDNA preparation.
In some embodiments, the methods include contacting the sample with an agent, e.g., an antibody, that binds specifically to an RNA-binding protein or protein complex such as PRC1, e.g., to CBX7.
In some embodiments, the methods include some or all of the following: isolating the complexes; synthesizing DNA complementary to the RNAs to provide an initial population of cDNAs; PCR-amplifying, if necessary, using strand-specific primers; purifying the initial population of cDNAs to obtain a purified population of cDNAs that are at least 20 nucleotides (nt) in length; and high-throughput sequencing the purified population of cDNAs. Homopolymer reads are filtered, and reads matching the mitochondrial genome and ribosomal RNAs are excluded from all subsequent analyses. Reads that align to a reference genome with <1 mismatch are retained, excluding homopolymers, reads that align to the mitochondrial genome, and ribosomal RNAs. High probability PRC1-interacting transcripts are then called based on criteria that reads were significantly enriched in the wildtype library versus control library (such as a protein-null or tag-only control library, a minus-crosslinking library, or library made from an IgG pulldown done in parallel) for any given transcript. For example, under one set of criteria published in Zhao et al., 2010, the transcripts were enriched 3:1 in the wildtype library over the EZH2-null library, and each transcript had an RPKM minimum of 0.4. The criteria can be adjusted up or down based on empirical control data suggesting what cutoffs could be reasonably used. Statistical methods may also be used to call enrichment or “peaks” (binding sites) in the PRC1 library relative to control libraries, as has been used for the peaks called herein.
In general, to construct dCLIP-seq libraries, RNAs are extracted from the gel using standard techniques. To capture all RNAs (not just polyA RNAs) and to preserve strand information, 3′end-specific adapter is ligated to the extracted RNA fragments followed by hybridization with reverse transcription primer specific to 3′end adaptor and ligation of second adaptor specific to 5′ end. The subsequent reverse transcription step creates first strand cDNA sequence that contains sequences complementary to the 3′ and 5′ adapters. The resulting PCR using 3′- and 5′-adaptor specific primer pairs is then performed to amplify the cDNAs and the products sequenced via standard methods of high throughput sequencing. Prior to sequencing, a size-selection step is incorporated in which amplified PCR products of desired sizes are excised after separation by gel electrophoresis (e.g., on a Nu-Sieve agarose gel or in an acrylamide gel) in order to remove an undesirable side products such as adapter dimers.
Kits
Provided herein are kits for use in the dCLIP-seq methods described herein. The kits can include, but are not limited to, an expression vector for expressing the bacterial biotin ligase BirA in a cell type of interest, and an expression vector for expressing RNA-binding proteins of interest, e.g., mammalian (e.g., human or mouse) RNA-binding proteins of interest PRC1 components such as CBX2, CBX4, CBX6, CBX7, CBX8, or RYPB fused in-frame to a Flag-biotinylation tag sequence. In addition to PRC1 components, PRC2 components (EZH2, EZH1, SUZ12, etc) or any other RNA-binding protein (ATRX, YY1, CTCF, as three examples) may be used as bait and fused in frame to the biotin tag. In some embodiments, the kits include buffers, e.g., a high stringency denaturing buffer, e.g., comprising 8 M urea (range: 5-10 M, 6-10M, 7-10M, 7-9M, or 7.5-8.5M) plus 0.1% SDS (range: 0.0-2.0%); wash buffer (e.g., PBS+2% SDS; high salt wash buffer (e.g., PBS+750 mM NaCl+1% NP40+0.5% NaDeoxycholate+0.1% SDS. Other detergents may be used as substitutes for SDS, including Triton X-100 and NP40; variations on salt conditions are also possible. In some embodiments, the kits include cells expressing BirA.
PRC1-Interacting RNAs and RNA Libraries
The present invention includes the individual PRC1-binding regions of RNAs described herein, as well as libraries of RNAs produced by methods described herein. In some embodiments, the libraries are in solution, or are lyophilized. In some embodiments, the libraries are bound to a substrate, e.g., wherein each member of the library is bound to an individually addressable member, e.g., an individual area on an array (e.g., a microarray), or a bead. The PRC1 RNA interactome consists of both coding and noncoding transcripts. Non-coding PRC1-interacting RNA transcripts may also include a protein-coding sequence of bases, e.g., a distinct transcript that overlaps in position with a protein-coding reference gene (e.g., the gene whose expression is modulated in cis).
In one embodiment, an RNA includes a nucleotide sequence that is at least about 85% or more homologous or identical to the entire length of an RNA sequence shown herein, e.g., in any of Tables 1-4, or a fragment comprising at least 20 nt thereof (e.g., at least 25, 30, 35, 40, 50, 60, 70, 80, 90, or 100 nt thereof, e.g., at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 50% or more of the full length RNA). In some embodiments, the nucleotide sequence is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% homologous or identical to an RNA sequence shown herein.
Mouse-to-human LiftOver analysis and analysis in the UCSC genome browser of syntenic positions indicate the existence of similar transcripts in the human genome. This process and LiftOver chains are generally described in Kent et al., Proc. Nat'l Acad. Sci., 100(20) 11484-11489 (2003). Given the geographic and sequence similarities between the mouse and human transcripts, we believe that a similar number of PRC1-interacting transcripts occur in the human system. The data suggest that many if not all of the mouse PRC1-transcripts have direct counterparts in the human epigenome. Such direct counterparts in other species are termed “orthologous” herein.
RNAs may be functionally conserved without being highly conserved at the level of overall nucleotide identity. For example, mouse Xist shows only 76% overall nucleotide identity with human XIST using sliding 21-bp windows, or an overall sequence identity of only 60%. However, within specific functional domains, the degree of conservation can be >70% between different mammalian species. The crucial motif in some RNAs (e.g., Repeat A of XIST) is the secondary structures formed by the repeat. An RNA interacting with PRC1 may therefore be similarly low in overall conservation but still have conservation in secondary structure within specific domains of the RNA, and thereby demonstrate functional conservation with respect to recruitment of PRC1.
Calculations of homology or sequence identity between sequences (the terms are used interchangeably herein) are performed as follows.
To determine the percent identity of two nucleic acid sequences, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). The length of a reference sequence aligned for comparison purposes is at least 80% of the length of the reference sequence, and in some embodiments is at least 90% or 100%. The nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position (as used herein nucleic acid “identity” is equivalent to nucleic acid “homology”). The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences.
For purposes of the present invention, the comparison of sequences and determination of percent identity between two sequences can be accomplished using a Blossum 62 scoring matrix with a gap penalty of 12, a gap extend penalty of 4, and a frameshift gap penalty of 5.
There are several potential uses for the RNAs described herein in the expanded PRC1 transcriptome: The RNAs themselves, or antagomirs and small molecules designed against them, can be utilized to modulate expression (either up or down) of Polycomb target genes.
In various related aspects, including with respect to the targeting of RNAs by LNA molecule, PRC1-binding RNAs can include endogenous coding and non-coding cellular RNAs, including but not limited to those RNAs that are greater than 60 nt in length, e.g., greater than 100 nt, e.g., greater than 200 nt, have no positive-strand open reading frames greater than 100 amino acids in length, are identified as ncRNAs by experimental evidence, and are distinct from known (smaller) functional-RNA classes (including but not limited to ribosomal, transfer, and small nuclear/nucleolar RNAs, siRNA, piRNA, and miRNA). See, e.g., Lipovich et al., “MacroRNA underdogs in a microRNA world: Evolutionary, regulatory, and biomedical significance of mammalian long non-protein-coding RNA” Biochimica et Biophysica Acta (2010) doi:10.1016/j.bbagrm.2010.10.001; Ponting et al., Cell 136(4):629-641 (2009), Jia et al., RNA 16 (8) (2010) 1478-1487, Dinger et al., Nucleic Acids Res. 37 1685 (2009) D122-D126 (database issue); and references cited therein. ncRNAs have also been referred to as, and can include, long non-coding RNA, long RNA, large RNA, macro RNA, intergenic RNA, and NonCoding Transcripts.
The methods described herein can be used to target both coding and non-coding RNAs. Known classes of RNAs include large intergenic non-coding RNAs (lincRNAs, see, e.g., Guttman et al., Nature. 2009 Mar. 12; 458(7235):223-7. Epub 2009 Feb. 1, which describes over a thousand exemplary highly conserved large non-coding RNAs in mammals; and Khalil et al., PNAS 106(28)₁₁₆₇₅-11680 (2009)); promoter associated short RNAs (PASRs; see, e.g., Seila et al., Science. 2008 Dec. 19; 322(5909):1849-51. Epub 2008 Dec. 4; Kanhere et al., Molecular Cell 38, 675-688, (2010)); endogenous antisense RNAs (see, e.g., Numata et al., BMC Genomics. 10:392 (2009); Okada et al., Hum Mol Genet. 17(11):1631-40 (2008); Numata et al., Gene 392(1-2):134-141 (2007); and Rosok and Sioud, Nat Biotechnol. 22(1):104-8 (2004)); and RNAs that bind chromatin modifiers such as PRC2 and LSD1 (see, e.g., Tsai et al., Science. 2010 Aug. 6; 329(5992):689-93. Epub 2010 Jul. 8; and Zhao et al., Science. 2008 Oct. 31; 322(5902):750-6).
Exemplary ncRNAs include XIST, TSIX, SRA1, and KCNQ1OT1. The sequences for more than 17,000 long human ncRNAs can be found in the NCode™ Long ncRNA Database on the Invitrogen website. Additional long ncRNAs can be identified using, e.g., manual published literature, Functional Annotation of Mouse (FANTOM3) project, Human Full-length cDNA Annotation Invitational (H-Invitational) project, antisense ncRNAs from cDNA and EST database for mouse and human using a computation pipeline (Zhang et al., Nucl. Acids Res. 35 (suppl 1): D156-D161 (2006); Engstrom et al., PLoS Genet. 2:e47 (2006)), human snoRNAs and scaRNAs derived from snoRNA-LBME-db, RNAz (Washietl et al. 2005), Noncoding RNA Search (Torarinsson, et al. 2006), and EvoFold (Pedersen et al. 2006).
Methods of Modulating Gene Expression
The RNAs described herein, including fragments thereof that are at least 20 nt in length, and inhibitory nucleic acids and small molecules targeting (e.g., complementary to) them, can be used to modulate gene expression in a cell, e.g., a cancer cell, a stem cell, or other normal cell types for gene or epigenetic therapy. The cells can be in vitro, including ex vivo, or in vivo (e.g., in a subject who has cancer, e.g., a tumor).
The methods described herein can be used for modulating expression of oncogenes and tumor suppressors in cells, e.g., cancer cells. For example, to decrease expression of an gene (e.g., an oncogene or imprinted gene) in a cell, the methods include introducing into the cell an inhibitory nucleic acid or small molecule that specifically binds, or is complementary, to a PRC1-binding region of an RNA that increases expression of the gene, e.g., an oncogene and/or an imprinted gene, set forth in Tables 1-3. As another example, to increase expression of a gene, e.g., a tumor suppressor, in a cell, the methods include introducing into the cell an inhibitory nucleic acid or small molecule that specifically binds, or is complementary, to a PRC1-binding region of an RNA that decreases expression of the gene, e.g., of a tumor suppressor gene, set forth in Tables 1-3, e.g., in subjects with cancer, e.g., lung adenocarcinoma patients.
In general, the methods include introducing into the cell an inhibitory nucleic acid that specifically binds, or is complementary, to a region of an RNA that modulated expression of a gene as set forth in Tables 1-3.
In preferred embodiments, the inhibitory nucleic acid binds to a region within or near (e.g., within 100, 200, 300, 400, 500, 600, 700, 1K, 2K, or 5K bases of) a PRC1-binding region of the RNA as set forth in Tables 1-3. The empirically-identified “peaks,” which are believed to represent PRC1-binding regions are shown in Table 1, with 500 nts of sequence on each side, so that in some the methods can include targeting a sequence as shown in one of the sequences in Tables 1-3, or a sequence that is between 500 nts from the start and 500 nts of the end of a sequence shown in Tables 1-3, or between 400 nts from the start and 400 nts of the end, 300 nts from the start and 300 nts of the end, between 200 nts from the start and 200 nts of the end, or between 100 nts from the start and 100 nts of the end, of a sequence shown in Tables 1-3. A nucleic acid that binds “specifically” binds primarily to the target RNA or related RNAs to inhibit regulatory function of the RNA but not of other non-target RNAs. The specificity of the nucleic acid interaction thus refers to its function (e.g., inhibiting the PRC1-associated repression of gene expression) rather than its hybridization capacity. Inhibitory nucleic acids may exhibit nonspecific binding to other sites in the genome or other RNAs, without interfering with binding of other regulatory proteins and without causing degradation of the non-specifically-bound RNA. Thus this nonspecific binding does not significantly affect function of other non-target RNAs and results in no significant adverse effects.
These methods can be used to treat a cancer in a subject by administering to the subject a composition (e.g., as described herein) comprising a PRC1-binding fragment of an RNA as described herein and/or an inhibitory nucleic acid that binds to an RNA (e.g., an inhibitory nucleic acid that binds to an RNA that inhibits a tumor suppressor, or cancer-suppressing gene, or imprinted gene and/or other growth-suppressing genes in any of Tables 1-3). Examples of cellular proliferative and/or differentiative disorders include cancer, e.g., carcinoma, sarcoma, metastatic disorders or hematopoietic neoplastic disorders, e.g., leukemias. A metastatic tumor can arise from a multitude of primary tumor types, including but not limited to those of prostate, colon, lung, breast and liver origin.
As used herein, treating includes “prophylactic treatment” which means reducing the incidence of or preventing (or reducing risk of) a sign or symptom of a disease in a patient at risk for the disease, and “therapeutic treatment”, which means reducing signs or symptoms of a disease, reducing progression of a disease, reducing severity of a disease, in a patient diagnosed with the disease. With respect to cancer, treating includes inhibiting tumor cell proliferation, increasing tumor cell death or killing, inhibiting rate of tumor cell growth or metastasis, reducing size of tumors, reducing number of tumors, reducing number of metastases, increasing 1-year or 5-year survival rate.
As used herein, the terms “cancer”, “hyperproliferative” and “neoplastic” refer to cells having the capacity for autonomous growth, i.e., an abnormal state or condition characterized by rapidly proliferating cell growth. Hyperproliferative and neoplastic disease states may be categorized as pathologic, i.e., characterizing or constituting a disease state, or may be categorized as non-pathologic, i.e., a deviation from normal but not associated with a disease state. The term is meant to include all types of cancerous growths or oncogenic processes, metastatic tissues or malignantly transformed cells, tissues, or organs, irrespective of histopathologic type or stage of invasiveness. “Pathologic hyperproliferative” cells occur in disease states characterized by malignant tumor growth. Examples of non-pathologic hyperproliferative cells include proliferation of cells associated with wound repair.
The terms “cancer” or “neoplasms” include malignancies of the various organ systems, such as affecting lung (e.g. small cell, non-small cell, squamous, adenocarcinoma), breast, thyroid, lymphoid, gastrointestinal, genito-urinary tract, kidney, bladder, liver (e.g. hepatocellular cancer), pancreas, ovary, cervix, endometrium, uterine, prostate, brain, as well as adenocarcinomas which include malignancies such as most colon cancers, colorectal cancer, renal-cell carcinoma, prostate cancer and/or testicular tumors, non-small cell carcinoma of the lung, cancer of the small intestine and cancer of the esophagus.
The term “carcinoma” is art recognized and refers to malignancies of epithelial or endocrine tissues including respiratory system carcinomas, gastrointestinal system carcinomas, genitourinary system carcinomas, testicular carcinomas, breast carcinomas, prostatic carcinomas, endocrine system carcinomas, and melanomas. In some embodiments, the disease is renal carcinoma or melanoma. Exemplary carcinomas include those forming from tissue of the cervix, lung, prostate, breast, head and neck, colon and ovary. The term also includes carcinosarcomas, e.g., which include malignant tumors composed of carcinomatous and sarcomatous tissues. An “adenocarcinoma” refers to a carcinoma derived from glandular tissue or in which the tumor cells form recognizable glandular structures.
The term “sarcoma” is art recognized and refers to malignant tumors of mesenchymal derivation.
Additional examples of proliferative disorders include hematopoietic neoplastic disorders. As used herein, the term “hematopoietic neoplastic disorders” includes diseases involving hyperplastic/neoplastic cells of hematopoietic origin, e.g., arising from myeloid, lymphoid or erythroid lineages, or precursor cells thereof. Preferably, the diseases arise from poorly differentiated acute leukemias, e.g., erythroblastic leukemia and acute megakaryoblastic leukemia. Additional exemplary myeloid disorders include, but are not limited to, acute promyeloid leukemia (APML), acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) (reviewed in Vaickus, L. (1991) Crit Rev. in Oncol./Hemotol. 11:267-97); lymphoid malignancies include, but are not limited to acute lymphoblastic leukemia (ALL) which includes B-lineage ALL and T-lineage ALL, chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), hairy cell leukemia (HLL) and Waldenstrom's macroglobulinemia (WM). Additional forms of malignant lymphomas include, but are not limited to non-Hodgkin lymphoma and variants thereof, peripheral T cell lymphomas, adult T cell leukemia/lymphoma (ATL), cutaneous T-cell lymphoma (CTCL), large granular lymphocytic leukemia (LGF), Hodgkin's disease and Reed-Sternberg disease.
In some embodiments, specific cancers that can be treated using the methods described herein include, but are not limited to: breast, lung, prostate, CNS (e.g., glioma), salivary gland, prostate, ovarian, and leukemias (e.g., ALL, CML, or AML). Associations of these genes with a particular cancer are known in the art, e.g., as described in Futreal et al., Nat Rev Cancer. 2004; 4; 177-83; and The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website, Bamford et al., Br J Cancer. 2004; 91; 355-8; see also Forbes et al., Curr Protoc Hum Genet. 2008; Chapter 10; Unit 10.11, and the COSMIC database, e.g., v. 50 (Nov. 30, 2010).
In addition, the methods described herein can be used for modulating (e.g., enhancing or decreasing) pluripotency of a stem cell and to direct stem cells down specific differentiation pathways to make endoderm, mesoderm, ectoderm, and their developmental derivatives. To increase, maintain, or enhance pluripotency, the methods include introducing into the cell an inhibitory nucleic acid that specifically binds to, or is complementary to, a PRC1-binding site on a non-coding RNA as set forth in any of Tables 1-3. Stem cells useful in the methods described herein include adult stem cells (e.g., adult stem cells obtained from the inner ear, bone marrow, mesenchyme, skin, fat, liver, muscle, or blood of a subject, e.g., the subject to be treated); embryonic stem cells, or stem cells obtained from a placenta or umbilical cord; progenitor cells (e.g., progenitor cells derived from the inner ear, bone marrow, mesenchyme, skin, fat, liver, muscle, or blood); and induced pluripotent stem cells (e.g., iPS cells).
Furthermore, the present methods can be used to treat Systemic Lupus erythematosus (SLE), an autoimmune disease that affects 1.5 million Americans (16,000 new cases per year). Ages 10-50 are the most affected, with more sufferers being female than male. SLE is a multi-organ disease; the effects include arthritis, joint pain & swelling, chest pain, fatigue, general malaise, hair loss, mouth sores, sensitivity to light, skin rash, and swollen lymph nodes. Current treatments include corticosteroids, immunosuppressants, and more recently belimumab (an inhibitor of B cell activating factor).
The causes of SLE are probably multiple, including HLA haplotypes. The interleukin 1 receptor associated kinase 1 (IRAK1) has been implicated in some patients. IRAK1 is X-linked (possibly explaining the female predominance of the disease) and is involved in immune response to foreign antigens and pathogens. IRAK1 has been associated with SLE in both adult and pediatric forms. Overexpression of IRAK1 in animal models causes SLE, and knocking out IRAK1 in mice alleviates symptoms of SLE. See, e.g., Jacob et al., Proc Natl Acad Sci USA. 2009 Apr. 14; 106(15):6256-61. The present methods can include treating a subject with SLE by administering an inhibitory nucleic acid that is complementary to a PRC1-binding region on IRAK1 RNA, e.g., an LNA targeting the 3′ UTR, e.g., as shown in Table 4.
The present methods can also be used to treat MECP2 Duplication Syndrome in a subject. This condition is characterized by mental retardation, weak muscle tone, and feeding difficulties, as well as poor/absent speech, seizures, and muscle spasticity. There are more reported cases in males than in females; female carriers may have skewed XCI. There is a 50% mortality rate by age 25 associated with this condition, which accounts for 1-2% of X-linked mental retardation. The real rate of incidence is unknown, as many go undiagnosed. Genetically, the cause is duplication (even triplication) of MECP2 gene. There is no current treatment. The present methods can include treating a subject with MECP2 Duplication Syndrome by administering an inhibitory nucleic acid that is complementary to a PRC1-binding region on Mecp2 RNA, e.g., an LNA targeting the 3′UTR of Mecp2 as shown in FIG. 2C, e.g., as shown in Table 4.
In some embodiments, the methods described herein include administering a composition, e.g., a sterile composition, comprising an inhibitory nucleic acid that is complementary to a PRC1-binding region on an RNA described herein, e.g., as set forth in any of Tables 1-3, or SEQ ID NOS:1-5893 (human) or 5894-17415 (human LiftOver). Inhibitory nucleic acids for use in practicing the methods described herein can be an antisense or small interfering RNA, including but not limited to an shRNA or siRNA. In some embodiments, the inhibitory nucleic acid is a modified nucleic acid polymer (e.g., a locked nucleic acid (LNA) molecule). The present methods can include administration of a
Inhibitory nucleic acids have been employed as therapeutic moieties in the treatment of disease states in animals, including humans. Inhibitory nucleic acids can be useful therapeutic modalities that can be configured to be useful in treatment regimes for the treatment of cells, tissues and animals, especially humans.
For therapeutics, an animal, preferably a human, suspected of having cancer is treated by administering an RNA or inhibitory nucleic acid in accordance with this invention. For example, in one non-limiting embodiment, the methods comprise the step of administering to the animal in need of treatment, a therapeutically effective amount of an RNA or inhibitory nucleic acid as described herein.
Inhibitory Nucleic Acids Inhibitory nucleic acids useful in the present methods and compositions include antisense oligonucleotides, ribozymes, external guide sequence (EGS) oligonucleotides, siRNA compounds, single- or double-stranded RNA interference (RNAi) compounds such as siRNA compounds, molecules comprising modified bases, locked nucleic acid molecules (LNA molecules), antagomirs, peptide nucleic acid molecules (PNA molecules), and other oligomeric compounds or oligonucleotide mimetics which hybridize to at least a portion of the target nucleic acid and modulate its function. In some embodiments, the inhibitory nucleic acids include antisense RNA, antisense DNA, chimeric antisense oligonucleotides, antisense oligonucleotides comprising modified linkages, interference RNA (RNAi), short interfering RNA (siRNA); a micro, interfering RNA (miRNA); a small, temporal RNA (stRNA); or a short, hairpin RNA (shRNA); small RNA-induced gene activation (RNAa); small activating RNAs (saRNAs), or combinations thereof. See, e.g., WO 2010040112.
In the present methods, the inhibitory nucleic acids are preferably designed to target a specific region of the RNA that binds to PRC1, as described herein (see Tables 1-3). These “inhibitory” nucleic acids are believed to work by inhibiting the interaction between the RNA and PRC1, and as described herein can be used to modulate expression of a gene.
In some embodiments, the inhibitory nucleic acids are 10 to 50, 13 to 50, or 13 to 30 nucleotides in length. One having ordinary skill in the art will appreciate that this embodies oligonucleotides having antisense (complementary) portions of 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 nucleotides in length, or any range therewithin. It is understood that non-complementary bases may be included in such inhibitory nucleic acids; for example, an inhibitory nucleic acid 30 nucleotides in length may have a portion of 15 bases that is complementary to the targeted RNA. In some embodiments, the oligonucleotides are 15 nucleotides in length. In some embodiments, the antisense or oligonucleotide compounds of the invention are 12 or 13 to 30 nucleotides in length. One having ordinary skill in the art will appreciate that this embodies inhibitory nucleic acids having antisense (complementary) portions of 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 nucleotides in length, or any range therewithin.
Preferably the inhibitory nucleic acid comprises one or more modifications comprising: a modified sugar moiety, and/or a modified internucleoside linkage, and/or a modified nucleotide and/or combinations thereof. It is not necessary for all positions in a given oligonucleotide to be uniformly modified, and in fact more than one of the modifications described herein may be incorporated in a single oligonucleotide or even at within a single nucleoside within an oligonucleotide.
In some embodiments, the inhibitory nucleic acids are chimeric oligonucleotides that contain two or more chemically distinct regions, each made up of at least one nucleotide. These oligonucleotides typically contain at least one region of modified nucleotides that confers one or more beneficial properties (such as, for example, increased nuclease resistance, increased uptake into cells, increased binding affinity for the target) and a region that is a substrate for enzymes capable of cleaving RNA:DNA or RNA:RNA hybrids. Chimeric inhibitory nucleic acids of the invention may be formed as composite structures of two or more oligonucleotides, modified oligonucleotides, oligonucleosides and/or oligonucleotide mimetics as described above. Such compounds have also been referred to in the art as hybrids or gapmers. Representative United States patents that teach the preparation of such hybrid structures comprise, but are not limited to, U.S. Pat. Nos. 5,013,830; 5,149,797; 5,220,007; 5,256,775; 5,366,878; 5,403,711; 5,491,133; 5,565,350; 5,623,065; 5,652,355; 5,652,356; and 5,700,922, each of which is herein incorporated by reference.
In some embodiments, the inhibitory nucleic acid comprises at least one nucleotide modified at the 2′ position of the sugar, most preferably a 2′-O-alkyl, 2′-O-alkyl-O-alkyl or 2′-fluoro-modified nucleotide. In other preferred embodiments, RNA modifications include 2′-fluoro, 2′-amino and 2′ O-methyl modifications on the ribose of pyrimidines, abasic residues or an inverted base at the 3′ end of the RNA. Such modifications are routinely incorporated into oligonucleotides and these oligonucleotides have been shown to have a higher Tm (i.e., higher target binding affinity) than; 2′-deoxyoligonucleotides against a given target.
A number of nucleotide and nucleoside modifications have been shown to make the oligonucleotide into which they are incorporated more resistant to nuclease digestion than the native oligodeoxynucleotide; these modified oligos survive intact for a longer time than unmodified oligonucleotides. Specific examples of modified oligonucleotides include those comprising modified backbones, for example, phosphorothioates, phosphotriesters, methyl phosphonates, short chain alkyl or cycloalkyl intersugar linkages or short chain heteroatomic or heterocyclic intersugar linkages. Most preferred are oligonucleotides with phosphorothioate backbones and those with heteroatom backbones, particularly CH₂—NH—O—CH₂, CH, ˜N(CH₃)˜O˜CH₂(known as a methylene(methylimino) or MMI backbone], CH₂—O—N(CH₃)—CH₂, CH₂—N(CH₃)—N(CH₃)—CH₂and 0-N(CH₃)— CH₂—CH₂backbones, wherein the native phosphodiester backbone is represented as O— P— O— CH); amide backbones (see De Mesmaeker et al. Ace. Chem. Res. 1995, 28:366-374); morpholino backbone structures (see Summerton and Weller, U.S. Pat. No. 5,034,506); peptide nucleic acid (PNA) backbone (wherein the phosphodiester backbone of the oligonucleotide is replaced with a polyamide backbone, the nucleotides being bound directly or indirectly to the aza nitrogen atoms of the polyamide backbone, see Nielsen et al., Science 1991, 254, 1497). Phosphorus-containing linkages include, but are not limited to, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates comprising 3′alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates comprising 3′-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3′-5′ to 5′-3′ or 2′-5′ to 5′-2′; see U.S. Pat. Nos. 3,687,808; 4,469,863; 4,476,301; 5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455, 233; 5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563, 253; 5,571,799; 5,587,361; and 5,625,050.
Morpholino-based oligomeric compounds are described in Dwaine A. Braasch and David R. Corey, Biochemistry, 2002, 41(14), 4503-4510); Genesis, volume 30, issue 3, 2001; Heasman, J., Dev. Biol., 2002, 243, 209-214; Nasevicius et al., Nat. Genet., 2000, 26, 216-220; Lacerra et al., Proc. Natl. Acad. Sci., 2000, 97, 9591-9596; and U.S. Pat. No. 5,034,506, issued Jul. 23, 1991. In some embodiments, the morpholino-based oligomeric compound is a phosphorodiamidate morpholino oligomer (PMO) (e.g., as described in Iverson, Curr. Opin. Mol. Ther., 3:235-238, 2001; and Wang et al., J. Gene Med., 12:354-364, 2010; the disclosures of which are incorporated herein by reference in their entireties).
Cyclohexenyl nucleic acid oligonucleotide mimetics are described in Wang et al., J. Am. Chem. Soc., 2000, 122, 8595-8602.
Modified oligonucleotide backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These comprise those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH2 component parts; see U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264, 562; 5, 264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; and 5,677,439, each of which is herein incorporated by reference.
Modified oligonucleotides are also known that include oligonucleotides that are based on or constructed from arabinonucleotide or modified arabinonucleotide residues. Arabinonucleosides are stereoisomers of ribonucleosides, differing only in the configuration at the 2′-position of the sugar ring. In some embodiments, a 2′-arabino modification is 2′-F arabino. In some embodiments, the modified oligonucleotide is 2′-fluoro-D-arabinonucleic acid (FANA) (as described in, for example, Lon et al., Biochem., 41:3457-3467, 2002 and Min et al., Bioorg. Med. Chem. Lett., 12:2651-2654, 2002; the disclosures of which are incorporated herein by reference in their entireties). Similar modifications can also be made at other positions on the sugar, particularly the 3′ position of the sugar on a 3′ terminal nucleoside or in 2′-5′ linked oligonucleotides and the 5′ position of 5′ terminal nucleotide.
PCT Publication No. WO 99/67378 discloses arabinonucleic acids (ANA) oligomers and their analogues for improved sequence specific inhibition of gene expression via association to complementary messenger RNA.
Other preferred modifications include ethylene-bridged nucleic acids (ENAs) (e.g., International Patent Publication No. WO 2005/042777, Morita et al., Nucleic Acid Res., Suppl 1:241-242, 2001; Surono et al., Hum. Gene Ther., 15:749-757, 2004; Koizumi, Curr. Opin. Mol. Ther., 8:144-149, 2006 and Horie et al., Nucleic Acids Symp. Ser (Oxf), 49:171-172, 2005; the disclosures of which are incorporated herein by reference in their entireties). Preferred ENAs include, but are not limited to, 2′-O,4′-C-ethylene-bridged nucleic acids.
Examples of LNAs are described in WO 2008/043753 and include compounds of the following formula.
where X and Y are independently selected among the groups —O—,
—S—, —N(H)—, N(R)—,—CH2- or —CH— (if part of a double bond),
—CH₂—O—, —CH₂—S—, —CH₂—N(H)—, —CH₂—N(R)—, —CH₂—CH₂— or —CH₂—CH— (if part of a double bond),
—CH═CH—, where R is selected from hydrogen and C_1-4-alkyl; Z and Z* are independently selected among an internucleoside linkage, a terminal group or a protecting group; B constitutes a natural or non-natural nucleotide base moiety; and the asymmetric groups may be found in either orientation.
Preferably, the LNA used in the oligomer of the invention comprises at least one LNA unit according any of the formulas
wherein Y is —O—, —S—, —NH—, or N(R^H); Z and Z* are independently selected among an internucleoside linkage, a terminal group or a protecting group; B constitutes a natural or non-natural nucleotide base moiety, and RH is selected from hydrogen and C_1-4-alkyl.
Preferably, the Locked Nucleic Acid (LNA) used in the oligomeric compound, such as an antisense oligonucleotide, of the invention comprises at least one nucleotide comprises a Locked Nucleic Acid (LNA) unit according any of the formulas shown in Scheme 2 of PCT/DK2006/000512.
Preferably, the LNA used in the oligomer of the invention comprises internucleoside linkages selected from -0-P(O)₂—O—, —O—P(O,S)—O—, -0-P(S)₂—O—, —S—P(O)₂—O—, —S—P(O,S)—O—, —S—P(S)₂—O—, -0-P(O)₂—S—, —O—P(O,S)—S—, —S—P(O)₂—S—, —O—PO(R^H)—O—, O—PO(OCH₃)—O—, —O—PO(NR^H)—O—, —O—PO(OCH₂CH₂S—R)—O—, —O—PO(BH₃)—O—, —O—PO(NHR^H)—O—, —O—P(O)₂—NR^H—, —NR^H—P(O)₂—O—, —NR^H—CO—O—, where R^His selected from hydrogen and C_1-4-alkyl.
Specifically preferred LNA units are shown in scheme 2:
The term “thio-LNA” comprises a locked nucleotide in which at least one of X or Y in the general formula above is selected from S or —CH2-S—. Thio-LNA can be in both beta-D and alpha-L-configuration.
The term “amino-LNA” comprises a locked nucleotide in which at least one of X or Y in the general formula above is selected from —N(H)—, N(R)—, CH₂—N(H)—, and —CH₂—N(R)— where R is selected from hydrogen and C_1-4-alkyl. Amino-LNA can be in both beta-D and alpha-L-configuration.
The term “oxy-LNA” comprises a locked nucleotide in which at least one of X or Y in the general formula above represents —O— or —CH₂—O—. Oxy-LNA can be in both beta-D and alpha-L-configuration.
The term “ena-LNA” comprises a locked nucleotide in which Y in the general formula above is —CH₂—O— (where the oxygen atom of —CH₂—O— is attached to the 2′-position relative to the base B).
LNAs are described in additional detail below.
One or more substituted sugar moieties can also be included, e.g., one of the following at the 2′ position: OH, SH, SCH₃, F, OCN, OCH₃OCH₃, OCH₃O(CH₂)n CH₃, O(CH₂)n NH₂or O(CH₂)n CH₃where n is from 1 to about 10; Ci to C10 lower alkyl, alkoxyalkoxy, substituted lower alkyl, alkaryl or aralkyl; Cl; Br; CN; CF3; OCF3; O—, S—, or N-alkyl; O-, S-, or N-alkenyl; SOCH3; SO2 CH3; ONO2; NO2; N3; NH2; heterocycloalkyl; heterocycloalkaryl; aminoalkylamino; polyalkylamino; substituted silyl; an RNA cleaving group; a reporter group; an intercalator; a group for improving the pharmacokinetic properties of an oligonucleotide; or a group for improving the pharmacodynamic properties of an oligonucleotide and other substituents having similar properties. A preferred modification includes 2′-methoxyethoxy [2′-O—CH₂CH₂OCH₃, also known as 2′-O-(2-methoxyethyl)] (Martin et al, Helv. Chim. Acta, 1995, 78, 486). Other preferred modifications include 2′-methoxy (2′-O—CH₃), 2′-propoxy (2′-OCH₂CH₂CH₃) and 2′-fluoro (2′-F). Similar modifications may also be made at other positions on the oligonucleotide, particularly the 3′ position of the sugar on the 3′ terminal nucleotide and the 5′ position of 5′ terminal nucleotide. Oligonucleotides may also have sugar mimetics such as cyclobutyls in place of the pentofuranosyl group.
Inhibitory nucleic acids can also include, additionally or alternatively, nucleobase (often referred to in the art simply as “base”) modifications or substitutions. As used herein, “unmodified” or “natural” nucleobases include adenine (A), guanine (G), thymine (T), cytosine (C) and uracil (U). Modified nucleobases include nucleobases found only infrequently or transiently in natural nucleic acids, e.g., hypoxanthine, 6-methyladenine, 5-Me pyrimidines, particularly 5-methylcytosine (also referred to as 5-methyl-2′ deoxycytosine and often referred to in the art as 5-Me-C), 5-hydroxymethylcytosine (HMC), glycosyl HMC and gentobiosyl HMC, isocytosine, pseudoisocytosine, as well as synthetic nucleobases, e.g., 2-aminoadenine, 2-(methylamino)adenine, 2-(imidazolylalkyl)adenine, 2-(aminoalklyamino)adenine or other heterosubstituted alkyladenines, 2-thiouracil, 2-thiothymine, 5-bromouracil, 5-hydroxymethyluracil, 5-propynyluracil, 8-azaguanine, 7-deazaguanine, N6 (6-aminohexyl)adenine, 6-aminopurine, 2-aminopurine, 2-chloro-6-aminopurine and 2,6-diaminopurine or other diaminopurines. See, e.g., Kornberg, “DNA Replication,” W. H. Freeman & Co., San Francisco, 1980, pp 75-77; and Gebeyehu, G., et al. Nucl. Acids Res., 15:4513 (1987)). A “universal” base known in the art, e.g., inosine, can also be included. 5-Me-C substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2<0>C. (Sanghvi, in Crooke, and Lebleu, eds., Antisense Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are presently preferred base substitutions.
It is not necessary for all positions in a given oligonucleotide to be uniformly modified, and in fact more than one of the modifications described herein may be incorporated in a single oligonucleotide or even at within a single nucleoside within an oligonucleotide.
In some embodiments, both a sugar and an internucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for hybridization with an appropriate nucleic acid target compound. One such oligomeric compound, an oligonucleotide mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA compounds, the sugar-backbone of an oligonucleotide is replaced with an amide containing backbone, for example, an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone. Representative United States patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Further teaching of PNA compounds can be found in Nielsen et al, Science, 1991, 254, 1497-1500.
Inhibitory nucleic acids can also include one or more nucleobase (often referred to in the art simply as “base”) modifications or substitutions. As used herein, “unmodified” or “natural” nucleobases comprise the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases comprise other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudo-uracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylquanine and 7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-deazaadenine.
Further, nucleobases comprise those disclosed in U.S. Pat. No. 3,687,808, those disclosed in “The Concise Encyclopedia of Polymer Science And Engineering”, pages 858-859, Kroschwitz, ed. John Wiley & Sons, 1990; those disclosed by Englisch et al., Angewandle Chemie, International Edition, 1991, 30, page 613, and those disclosed by Sanghvi, Chapter 15, Antisense Research and Applications,” pages 289-302, Crooke, and Lebleu, eds., CRC Press, 1993. Certain of these nucleobases are particularly useful for increasing the binding affinity of the oligomeric compounds of the invention. These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6 substituted purines, comprising 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2<0>C (Sanghvi, et al., eds, “Antisense Research and Applications,” CRC Press, Boca Raton, 1993, pp. 276-278) and are presently preferred base substitutions, even more particularly when combined with 2′-O-methoxyethyl sugar modifications. Modified nucleobases are described in U.S. Pat. No. 3,687,808, as well as U.S. Pat. Nos. 4,845,205; 5,130,302; 5,134,066; 5,175, 273; 5, 367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908; 5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,596,091; 5,614,617; 5,750,692, and 5,681,941, each of which is herein incorporated by reference.
In some embodiments, the inhibitory nucleic acids are chemically linked to one or more moieties or conjugates that enhance the activity, cellular distribution, or cellular uptake of the oligonucleotide. For example, one or more inhibitory nucleic acids, of the same or different types, can be conjugated to each other; or inhibitory nucleic acids can be conjugated to targeting moieties with enhanced specificity for a cell type or tissue type. Such moieties include, but are not limited to, lipid moieties such as a cholesterol moiety (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989, 86, 6553-6556), cholic acid (Manoharan et al., Bioorg. Med. Chem. Let., 1994, 4, 1053-1060), a thioether, e.g., hexyl-S— tritylthiol (Manoharan et al, Ann. N. Y. Acad. Sci., 1992, 660, 306-309; Manoharan et al., Bioorg. Med. Chem. Let., 1993, 3, 2765-2770), a thiocholesterol (Oberhauser et al., Nucl. Acids Res., 1992, 20, 533-538), an aliphatic chain, e.g., dodecandiol or undecyl residues (Kabanov et al., FEBS Lett., 1990, 259, 327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654; Shea et al., Nucl. Acids Res., 1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain (Mancharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264, 229-237), or an octadecylamine or hexylamino-carbonyl-t oxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277, 923-937). See also U.S. Pat. Nos. 4,828,979; 4,948,882; 5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552, 538; 5,578,717, 5,580,731; 5,580,731; 5,591,584; 5,109,124; 5,118,802; 5,138,045; 5,414,077; 5,486, 603; 5,512,439; 5,578,718; 5,608,046; 4,587,044; 4,605,735; 4,667,025; 4,762, 779; 4,789,737; 4,824,941; 4,835,263; 4,876,335; 4,904,582; 4,958,013; 5,082, 830; 5,112,963; 5,214,136; 5,082,830; 5,112,963; 5,214,136; 5, 245,022; 5,254,469; 5,258,506; 5,262,536; 5,272,250; 5,292,873; 5,317,098; 5,371,241, 5,391, 723; 5,416,203, 5,451,463; 5,510,475; 5,512,667; 5,514,785; 5, 565,552; 5,567,810; 5,574,142; 5,585,481; 5,587,371; 5,595,726; 5,597,696; 5,599,923; 5,599, 928 and 5,688,941, each of which is herein incorporated by reference.
These moieties or conjugates can include conjugate groups covalently bound to functional groups such as primary or secondary hydroxyl groups. Conjugate groups of the invention include intercalators, reporter molecules, polyamines, polyamides, polyethylene glycols, polyethers, groups that enhance the pharmacodynamic properties of oligomers, and groups that enhance the pharmacokinetic properties of oligomers. Typical conjugate groups include cholesterols, lipids, phospholipids, biotin, phenazine, folate, phenanthridine, anthraquinone, acridine, fluoresceins, rhodamines, coumarins, and dyes. Groups that enhance the pharmacodynamic properties, in the context of this invention, include groups that improve uptake, enhance resistance to degradation, and/or strengthen sequence-specific hybridization with the target nucleic acid. Groups that enhance the pharmacokinetic properties, in the context of this invention, include groups that improve uptake, distribution, metabolism or excretion of the compounds of the present invention. Representative conjugate groups are disclosed in International Patent Application No. PCT/US92/09196, filed Oct. 23, 1992, and U.S. Pat. No. 6,287,860, which are incorporated herein by reference. Conjugate moieties include, but are not limited to, lipid moieties such as a cholesterol moiety, cholic acid, a thioether, e.g., hexyl-5-tritylthiol, a thiocholesterol, an aliphatic chain, e.g., dodecandiol or undecyl residues, a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate, a polyamine or a polyethylene glycol chain, or adamantane acetic acid, a palmityl moiety, or an octadecylamine or hexylamino-carbonyl-oxy cholesterol moiety. See, e.g., U.S. Pat. Nos. 4,828,979; 4,948,882; 5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552,538; 5,578,717, 5,580,731; 5,580,731; 5,591,584; 5,109,124; 5,118,802; 5,138,045; 5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044; 4,605,735; 4,667,025; 4,762,779; 4,789,737; 4,824,941; 4,835,263; 4,876,335; 4,904,582; 4,958,013; 5,082,830; 5,112,963; 5,214,136; 5,082,830; 5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506; 5,262,536; 5,272,250; 5,292,873; 5,317,098; 5,371,241, 5,391,723; 5,416,203, 5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552; 5,567,810; 5,574,142; 5,585,481; 5,587,371; 5,595,726; 5,597,696; 5,599,923; 5,599,928 and 5,688,941.
The inhibitory nucleic acids useful in the present methods are sufficiently complementary to the target RNA, e.g., hybridize sufficiently well and with sufficient biological functional specificity, to give the desired effect. “Complementary” refers to the capacity for pairing, through base stacking and specific hydrogen bonding, between two sequences comprising naturally or non-naturally occurring (e.g., modified as described above) bases (nucleosides) or analogs thereof. For example, if a base at one position of an inhibitory nucleic acid is capable of hydrogen bonding with a base at the corresponding position of an RNA, then the bases are considered to be complementary to each other at that position. 100% complementarity is not required. As noted above, inhibitory nucleic acids can comprise universal bases, or inert abasic spacers that provide no positive or negative contribution to hydrogen bonding. Base pairings may include both canonical Watson-Crick base pairing and non-Watson-Crick base pairing (e.g., Wobble base pairing and Hoogsteen base pairing). It is understood that for complementary base pairings, adenosine-type bases (A) are complementary to thymidine-type bases (T) or uracil-type bases (U), that cytosine-type bases (C) are complementary to guanosine-type bases (G), and that universal bases such as such as 3-nitropyrrole or 5-nitroindole can hybridize to and are considered complementary to any A, C, U, or T. Nichols et al., Nature, 1994; 369:492-493 and Loakes et al., Nucleic Acids Res., 1994; 22:4039-4043. Inosine (I) has also been considered in the art to be a universal base and is considered complementary to any A, C, U, or T. See Watkins and SantaLucia, Nucl. Acids Research, 2005; 33 (19): 6258-6267.
In some embodiments, the location on a target RNA to which an inhibitory nucleic acids hybridizes is defined as a region to which a protein binding partner binds, as shown in Tables 1-3. Routine methods can be used to design an inhibitory nucleic acid that binds to this sequence with sufficient specificity. In some embodiments, the methods include using bioinformatics methods known in the art to identify regions of secondary structure, e.g., one, two, or more stem-loop structures, or pseudoknots, and selecting those regions to target with an inhibitory nucleic acid. For example, methods of designing oligonucleotides similar to the inhibitory nucleic acids described herein, and various options for modified chemistries or formats, are exemplified in Lennox and Behlke, Gene Therapy (2011) 18: 1111-1120, which is incorporated herein by reference in its entirety, with the understanding that the present disclosure does not target miRNA ‘seed regions’.
While the specific sequences of certain exemplary target segments are set forth herein, one of skill in the art will recognize that these serve to illustrate and describe particular embodiments within the scope of the present invention. Additional target segments are readily identifiable by one having ordinary skill in the art in view of this disclosure. Target segments 5-500 nucleotides in length comprising a stretch of at least five (5) consecutive nucleotides within the protein binding region, or immediately adjacent thereto, are considered to be suitable for targeting as well. Target segments can include sequences that comprise at least the 5 consecutive nucleotides from the 5 ‘-terminus of one of the protein binding regions (the remaining nucleotides being a consecutive stretch of the same RNA beginning immediately upstream of the 5’-terminus of the binding segment and continuing until the inhibitory nucleic acid contains about 5 to about 100 nucleotides). Similarly preferred target segments are represented by RNA sequences that comprise at least the 5 consecutive nucleotides from the 3 ‘-terminus of one of the illustrative preferred target segments (the remaining nucleotides being a consecutive stretch of the same RNA beginning immediately downstream of the 3’-terminus of the target segment and continuing until the inhibitory nucleic acid contains about 5 to about 100 nucleotides). One having skill in the art armed with the sequences provided herein will be able, without undue experimentation, to identify further preferred protein binding regions to target with complementary inhibitory nucleic acids.
In the context of the present disclosure, hybridization means base stacking and hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleoside or nucleotide bases. For example, adenine and thymine are complementary nucleobases which pair through the formation of hydrogen bonds. Complementary, as the term is used in the art, refers to the capacity for precise pairing between two nucleotides. For example, if a nucleotide at a certain position of an oligonucleotide is capable of hydrogen bonding with a nucleotide at the same position of a RNA molecule, then the inhibitory nucleic acid and the RNA are considered to be complementary to each other at that position. The inhibitory nucleic acids and the RNA are complementary to each other when a sufficient number of corresponding positions in each molecule are occupied by nucleotides that can hydrogen bond with each other through their bases. Thus, “specifically hybridizable” and “complementary” are terms which are used to indicate a sufficient degree of complementarity or precise pairing such that stable and specific binding occurs between the inhibitory nucleic acid and the RNA target. For example, if a base at one position of an inhibitory nucleic acid is capable of hydrogen bonding with a base at the corresponding position of a RNA, then the bases are considered to be complementary to each other at that position. 100% complementarity is not required.
It is understood in the art that a complementary nucleic acid sequence need not be 100% complementary to that of its target nucleic acid to be specifically hybridizable. A complementary nucleic acid sequence for purposes of the present methods is specifically hybridizable when binding of the sequence to the target RNA molecule interferes with the normal function of the target RNA to cause a loss of activity (e.g., inhibiting PRC1-associated repression with consequent up-regulation of gene expression) and there is a sufficient degree of complementarity to avoid non-specific binding of the sequence to non-target RNA sequences under conditions in which avoidance of the non-specific binding is desired, e.g., under physiological conditions in the case of in vivo assays or therapeutic treatment, and in the case of in vitro assays, under conditions in which the assays are performed under suitable conditions of stringency. For example, stringent salt concentration will ordinarily be less than about 750 mM NaCl and 75 mM trisodium citrate, preferably less than about 500 mM NaCl and 50 mM trisodium citrate, and more preferably less than about 250 mM NaCl and 25 mM trisodium citrate. Low stringency hybridization can be obtained in the absence of organic solvent, e.g., formamide, while high stringency hybridization can be obtained in the presence of at least about 35% formamide, and more preferably at least about 50% formamide. Stringent temperature conditions will ordinarily include temperatures of at least about 30° C., more preferably of at least about 37° C., and most preferably of at least about 42° C. Varying additional parameters, such as hybridization time, the concentration of detergent, e.g., sodium dodecyl sulfate (SDS), and the inclusion or exclusion of carrier DNA, are well known to those skilled in the art. Various levels of stringency are accomplished by combining these various conditions as needed. In a preferred embodiment, hybridization will occur at 30° C. in 750 mM NaCl, 75 mM trisodium citrate, and 1% SDS. In a more preferred embodiment, hybridization will occur at 37° C. in 500 mM NaCl, 50 mM trisodium citrate, 1% SDS, 35% formamide, and 100 μg/ml denatured salmon sperm DNA (ssDNA). In a most preferred embodiment, hybridization will occur at 42° C. in 250 mM NaCl, 25 mM trisodium citrate, 1% SDS, 50% formamide, and 200 μg/ml ssDNA. Useful variations on these conditions will be readily apparent to those skilled in the art.
For most applications, washing steps that follow hybridization will also vary in stringency. Wash stringency conditions can be defined by salt concentration and by temperature. As above, wash stringency can be increased by decreasing salt concentration or by increasing temperature. For example, stringent salt concentration for the wash steps will preferably be less than about 30 mM NaCl and 3 mM trisodium citrate, and most preferably less than about 15 mM NaCl and 1.5 mM trisodium citrate. Stringent temperature conditions for the wash steps will ordinarily include a temperature of at least about 25° C., more preferably of at least about 42° C., and even more preferably of at least about 68° C. In a preferred embodiment, wash steps will occur at 25° C. in 30 mM NaCl, 3 mM trisodium citrate, and 0.1% SDS. In a more preferred embodiment, wash steps will occur at 42° C. in 15 mM NaCl, 1.5 mM trisodium citrate, and 0.1% SDS. In a more preferred embodiment, wash steps will occur at 68° C. in 15 mM NaCl, 1.5 mM trisodium citrate, and 0.1% SDS. Additional variations on these conditions will be readily apparent to those skilled in the art. Hybridization techniques are well known to those skilled in the art and are described, for example, in Benton and Davis (Science 196:180, 1977); Grunstein and Hogness (Proc. Natl. Acad. Sci., USA 72:3961, 1975); Ausubel et al. (Current Protocols in Molecular Biology, Wiley Interscience, New York, 2001); Berger and Kimmel (Guide to Molecular Cloning Techniques, 1987, Academic Press, New York); and Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, New York.
In general, the inhibitory nucleic acids useful in the methods described herein have at least 80% sequence complementarity to a target region within the target nucleic acid, e.g., 90%, 95%, or 100% sequence complementarity to the target region within an RNA. For example, an antisense compound in which 18 of 20 nucleobases of the antisense oligonucleotide are complementary, and would therefore specifically hybridize, to a target region would represent 90 percent complementarity. Percent complementarity of an inhibitory nucleic acid with a region of a target nucleic acid can be determined routinely using basic local alignment search tools (BLAST programs) (Altschul et al., J. Mol. Biol., 1990, 215, 403-410; Zhang and Madden, Genome Res., 1997, 7, 649-656). Antisense and other compounds of the invention that hybridize to an RNA are identified through routine experimentation. In general the inhibitory nucleic acids must retain specificity for their target, i.e., either do not directly bind to, or do not directly significantly affect expression levels of, transcripts other than the intended target.
Target-specific effects, with corresponding target-specific functional biological effects, are possible even when the inhibitory nucleic acid exhibits non-specific binding to a large number of non-target RNAs. For example, short 8 base long inhibitory nucleic acids that are fully complementary to a RNA may have multiple 100% matches to hundreds of sequences in the genome, yet may produce target-specific effects, e.g. upregulation of a specific target gene through inhibition of PRC1 activity. 8-base inhibitory nucleic acids have been reported to prevent exon skipping with with a high degree of specificity and reduced off-target effect. See Singh et al., RNA Biol., 2009; 6(3): 341-350. 8-base inhibitory nucleic acids have been reported to interfere with miRNA activity without significant off-target effects. See Obad et al., Nature Genetics, 2011; 43: 371-378.
For further disclosure regarding inhibitory nucleic acids, please see US2010/0317718 (antisense oligos); US2010/0249052 (double-stranded ribonucleic acid (dsRNA)); US2009/0181914 and US2010/0234451 (LNA molecules); US2007/0191294 (siRNA analogues); US2008/0249039 (modified siRNA); and WO2010/129746 and WO2010/040112 (inhibitory nucleic acids).
Antisense
In some embodiments, the inhibitory nucleic acids are antisense oligonucleotides. Antisense oligonucleotides are typically designed to block expression of a DNA or RNA target by binding to the target and halting expression at the level of transcription, translation, or splicing. Antisense oligonucleotides of the present invention are complementary nucleic acid sequences designed to hybridize under stringent conditions to an RNA in vitro, and are expected to inhibit the activity of PRC1 in vivo. Thus, oligonucleotides are chosen that are sufficiently complementary to the target, i.e., that hybridize sufficiently well and with sufficient biological functional specificity, to give the desired effect.
Modified Base, Including Locked Nucleic Acids (LNAs)
In some embodiments, the inhibitory nucleic acids used in the methods described herein comprise one or more modified bonds or bases. Modified bases include phosphorothioate, methylphosphonate, peptide nucleic acids, or locked nucleic acids (LNAs). Preferably, the modified nucleotides are part of locked nucleic acid molecules, including [alpha]-L-LNAs. LNAs include ribonucleic acid analogues wherein the ribose ring is “locked” by a methylene bridge between the 2′-oxgygen and the 4′-carbon—i.e., oligonucleotides containing at least one LNA monomer, that is, one 2′-O,4′-C-methylene-β-D-ribofuranosyl nucleotide. LNA bases form standard Watson-Crick base pairs but the locked configuration increases the rate and stability of the basepairing reaction (Jepsen et al., Oligonucleotides, 14, 130-146 (2004)). LNAs also have increased affinity to base pair with RNA as compared to DNA. These properties render LNAs especially useful as probes for fluorescence in situ hybridization (FISH) and comparative genomic hybridization, as knockdown tools for miRNAs, and as antisense oligonucleotides to target mRNAs or other RNAs, e.g., RNAs as described herien.
The modified base/LNA molecules can include molecules comprising 10-30, e.g., 12-24, e.g., 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in each strand, wherein one of the strands is substantially identical, e.g., at least 80% (or more, e.g., 85%, 90%, 95%, or 100%) identical, e.g., having 3, 2, 1, or 0 mismatched nucleotide(s), to a target region in the RNA. The modified base/LNA molecules can be chemically synthesized using methods known in the art.
The modified base/LNA molecules can be designed using any method known in the art; a number of algorithms are known, and are commercially available (e.g., on the internet, for example at exiqon.com). See, e.g., You et al., Nuc. Acids. Res. 34:e60 (2006); McTigue et al., Biochemistry 43:5388-405 (2004); and Levin et al., Nuc. Acids. Res. 34:e142 (2006). For example, “gene walk” methods, similar to those used to design antisense oligos, can be used to optimize the inhibitory activity of a modified base/LNA molecule; for example, a series of oligonucleotides of 10-30 nucleotides spanning the length of a target RNA can be prepared, followed by testing for activity. Optionally, gaps, e.g., of 5-10 nucleotides or more, can be left between the LNAs to reduce the number of oligonucleotides synthesized and tested. GC content is preferably between about 30₇60%. General guidelines for designing modified base/LNA molecules are known in the art; for example, LNA sequences will bind very tightly to other LNA sequences, so it is preferable to avoid significant complementarity within an LNA molecule. Contiguous runs of three or more Gs or Cs, or more than four LNA residues, should be avoided where possible (for example, it may not be possible with very short (e.g., about 9-10 nt) oligonucleotides). In some embodiments, the LNAs are xylo-LNAs.
For additional information regarding LNA molecules see U.S. Pat. Nos. 6,268,490; 6,734,291; 6,770,748; 6,794,499; 7,034,133; 7,053,207; 7,060,809; 7,084,125; and 7,572,582; and U.S. Pre-Grant Pub. Nos. 20100267018; 20100261175; and 20100035968; Koshkin et al. Tetrahedron 54, 3607-3630 (1998); Obika et al. Tetrahedron Lett. 39, 5401-5404 (1998); Jepsen et al., Oligonucleotides 14:130-146 (2004); Kauppinen et al., Drug Disc. Today 2(3):287-290 (2005); and Ponting et al., Cell 136(4):629-641 (2009), and references cited therein.
As demonstrated herein and previously (see, e.g., WO 2012/065143 and WO 2012/087983, incorporated herein by reference), LNA molecules can be used as a valuable tool to manipulate and aid analysis of RNAs. Advantages offered by an LNA molecule-based system are the relatively low costs, easy delivery, and rapid action. While other inhibitory nucleic acids may exhibit effects after longer periods of time, LNA molecules exhibit effects that are more rapid, e.g., a comparatively early onset of activity, are fully reversible after a recovery period following the synthesis of new RNA, and occur without causing substantial or substantially complete RNA cleavage or degradation. One or more of these design properties may be desired properties of the inhibitory nucleic acids of the invention. Additionally, LNA molecules make possible the systematic targeting of domains within much longer nuclear transcripts. Although a PNA-based system has been described earlier, the effects on Xi were apparent only after 24 hours (Beletskii et al., Proc Natl Acad Sci USA. 2001; 98:9215-9220). The LNA technology enables high-throughput screens for functional analysis of non-coding RNAs and also provides a novel tool to manipulate chromatin states in vivo for therapeutic applications.
In various related aspects, the methods described herein include using LNA molecules to target RNAs for a number of uses, including as a research tool to probe the function of a specific RNA, e.g., in vitro or in vivo. The methods include selecting one or more desired RNAs, designing one or more LNA molecules that target the RNA, providing the designed LNA molecule, and administering the LNA molecule to a cell or animal. The methods can optionally include selecting a region of the RNA and designing one or more LNA molecules that target that region of the RNA.
Aberrant imprinted gene expression is implicated in several diseases including Long QT syndrome, Beckwith-Wiedemann, Prader-Willi, and Angelman syndromes, as well as behavioral disorders and carcinogenesis (see, e.g., Falls et al., Am. J. Pathol. 154:635-647 (1999); Lalonde, Annu Rev Genet 30:173-195 (1996); Hall Annu Rev Med. 48:35-44 (1997)). LNA molecules can be created to treat such imprinted diseases. As one example, the long QT Syndrome can be caused by a K+ gated Calcium-channel encoded by Kcnql. This gene is regulated by its antisense counterpart, the long noncoding RNA, Kcnqlotl (Pandey et al., Mol Cell. 2008 Oct. 24; 32(2):232-46). Disease arises when Kcnqlotl is aberrantly expressed. LNA molecules can be created to downregulate Kcnqlotl, thereby restoring expression of Kcnql. As another example, LNA molecules could inhibit RNA cofactors for polycomb complex chromatin modifiers to reverse the imprinted defect.
From a commercial and clinical perspective, the timepoints between about 1 to 24 hours potentially define a window for epigenetic reprogramming. The advantage of the LNA system is that it works quickly, with a defined half-life, and is therefore reversible upon degradation of LNAs, at the same time that it provides a discrete timeframe during which epigenetic manipulations can be made. By targeting nuclear long RNAs, LNA molecules or similar polymers, e.g., xylo-LNAs, might be utilized to manipulate the chromatin state of cells in culture or in vivo, by transiently eliminating the regulatory RNA and associated proteins long enough to alter the underlying locus for therapeutic purposes. In particular, LNA molecules or similar polymers that specifically bind to, or are complementary to, PRC1-binding RNA can prevent recruitment of PRC1 to a specific chromosomal locus, in a gene-specific fashion.
LNA molecules might also be administered in vivo to treat other human diseases, such as but not limited to cancer, neurological disorders, infections, inflammation, and myotonic dystrophy. For example, LNA molecules might be delivered to tumor cells to downregulate the biologic activity of a growth-promoting or oncogenic long nuclear RNA (e.g., Gt12 or MALAT1 (Luo et al., Hepatology. 44(4):1012-24 (2006)), a RNA associated with metastasis and is frequently upregulated in cancers). Repressive RNAs downregulating tumor suppressors can also be targeted by LNA molecules to promote reexpression. For example, expression of the INK4b/ARF/INK4a tumor suppressor locus is controlled by Polycomb group proteins including PRC1 and PRC1 and repressed by the antisense noncoding RNA ANRIL (Yap et al., Mol Cell. 2010 Jun. 11; 38(5):662-74). PRC1-binding regions described herein in ANRIL can be targeted by LNA molecules to promote reexpression of the INK4b/ARF/INK4a tumor suppressor. Some ncRNAs may be positive regulators of oncogenes. Such “activating ncRNAs” have been described recently (e.g., Jpx (Tian et al., Cell. 143(3):390-403 (2010) and others (from et al., Cell. 143(1):46-58 (2010)). Therefore, LNA molecules could be directed at these activating ncRNAs to downregulate oncogenes. LNA molecules could also be delivered to inflammatory cells to downregulate regulatory ncRNA that modulate the inflammatory or immune response. (e.g., LincRNA-Cox2, see Guttman et al., Nature. 458(7235):223-7. Epub 2009 Feb. 1 (2009)).
In still other related aspects, the LNA molecules targeting PRC1-binding regions in RNAs described herein can be used to create animal or cell models of conditions associated with altered gene expression (e.g., as a result of altered epigenetics).
The methods described herein may also be useful for creating animal or cell models of other conditions associated with aberrant imprinted gene expression, e.g., as noted above.
In various related aspects, the results described herein demonstrate the utility of LNA molecules for targeting RNA, for example, to transiently disrupt chromatin for purposes of reprogramming chromatin states ex vivo. Because LNA molecules stably displace RNA for hours and chromatin does not rebuild for hours thereafter, LNA molecules create a window of opportunity to manipulate the epigenetic state of specific loci ex vivo, e.g., for reprogramming of hiPS and hESC prior to stem cell therapy. For example, Gt12 controls expression of DLK1, which modulates the pluripotency of iPS cells. Low Gt12 and high DLK1 is correlated with increased pluripotency and stability in human iPS cells. Thus, LNA molecules targeting Gt12 can be used to inhibit differentiation and increase pluripotency and stability of iPS cells.
See also PCT/US11/60493, which is incorporated by reference herein in its entirety.
Interfering RNA, Including siRNA/shRNA
In some embodiments, the inhibitory nucleic acid sequence that is complementary to an RNA can be an interfering RNA, including but not limited to a small interfering RNA (“siRNA”) or a small hairpin RNA (“shRNA”). Methods for constructing interfering RNAs are well known in the art. For example, the interfering RNA can be assembled from two separate oligonucleotides, where one strand is the sense strand and the other is the antisense strand, wherein the antisense and sense strands are self-complementary (i.e., each strand comprises nucleotide sequence that is complementary to nucleotide sequence in the other strand; such as where the antisense strand and sense strand form a duplex or double stranded structure); the antisense strand comprises nucleotide sequence that is complementary to a nucleotide sequence in a target nucleic acid molecule or a portion thereof (i.e., an undesired gene) and the sense strand comprises nucleotide sequence corresponding to the target nucleic acid sequence or a portion thereof. Alternatively, interfering RNA is assembled from a single oligonucleotide, where the self-complementary sense and antisense regions are linked by means of nucleic acid based or non-nucleic acid-based linker(s). The interfering RNA can be a polynucleotide with a duplex, asymmetric duplex, hairpin or asymmetric hairpin secondary structure, having self-complementary sense and antisense regions, wherein the antisense region comprises a nucleotide sequence that is complementary to nucleotide sequence in a separate target nucleic acid molecule or a portion thereof and the sense region having nucleotide sequence corresponding to the target nucleic acid sequence or a portion thereof. The interfering can be a circular single-stranded polynucleotide having two or more loop structures and a stem comprising self-complementary sense and antisense regions, wherein the antisense region comprises nucleotide sequence that is complementary to nucleotide sequence in a target nucleic acid molecule or a portion thereof and the sense region having nucleotide sequence corresponding to the target nucleic acid sequence or a portion thereof, and wherein the circular polynucleotide can be processed either in vivo or in vitro to generate an active siRNA molecule capable of mediating RNA interference.
In some embodiments, the interfering RNA coding region encodes a self-complementary RNA molecule having a sense region, an antisense region and a loop region. Such an RNA molecule when expressed desirably forms a “hairpin” structure, and is referred to herein as an “shRNA.” The loop region is generally between about 2 and about 10 nucleotides in length. In some embodiments, the loop region is from about 6 to about 9 nucleotides in length. In some embodiments, the sense region and the antisense region are between about 15 and about 20 nucleotides in length. Following post-transcriptional processing, the small hairpin RNA is converted into a siRNA by a cleavage event mediated by the enzyme Dicer, which is a member of the RNase III family. The siRNA is then capable of inhibiting the expression of a gene with which it shares homology. For details, see Brummelkamp et al., Science 296:550-553, (2002); Lee et al, Nature Biotechnol., 20, 500-505, (2002); Miyagishi and Taira, Nature Biotechnol 20:497-500, (2002); Paddison et al. Genes & Dev. 16:948-958, (2002); Paul, Nature Biotechnol, 20, 505-508, (2002); Sui, Proc. Natl. Acad. Sd. USA, 99(6), 5515-5520, (2002); Yu et al. Proc NatlAcadSci USA 99:6047-6052, (2002).
The target RNA cleavage reaction guided by siRNAs is highly sequence specific. In general, siRNA containing a nucleotide sequences identical to a portion of the target nucleic acid are preferred for inhibition. However, 100% sequence identity between the siRNA and the target gene is not required to practice the present invention. Thus the invention has the advantage of being able to tolerate sequence variations that might be expected due to genetic mutation, strain polymorphism, or evolutionary divergence. For example, siRNA sequences with insertions, deletions, and single point mutations relative to the target sequence have also been found to be effective for inhibition. Alternatively, siRNA sequences with nucleotide analog substitutions or insertions can be effective for inhibition. In general the siRNAs must retain specificity for their target, i.e., must not directly bind to, or directly significantly affect expression levels of, transcripts other than the intended target.
Ribozymes
In some embodiments, the inhibitory nucleic acids are ribozymes. Trans-cleaving enzymatic nucleic acid molecules can also be used; they have shown promise as therapeutic agents for human disease (Usman & McSwiggen, 1995 Ann. Rep. Med. Chem. 30, 285-294; Christoffersen and Marr, 1995 J. Med. Chem. 38, 2023-2037). Enzymatic nucleic acid molecules can be designed to cleave specific RNA targets within the background of cellular RNA. Such a cleavage event renders the RNA non-functional.
In general, enzymatic nucleic acids with RNA cleaving activity act by first binding to a target RNA. Such binding occurs through the target binding portion of a enzymatic nucleic acid which is held in close proximity to an enzymatic portion of the molecule that acts to cleave the target RNA. Thus, the enzymatic nucleic acid first recognizes and then binds a target RNA through complementary base pairing, and once bound to the correct site, acts enzymatically to cut the target RNA. Strategic cleavage of such a target RNA will destroy its ability to direct synthesis of an encoded protein. After an enzymatic nucleic acid has bound and cleaved its RNA target, it is released from that RNA to search for another target and can repeatedly bind and cleave new targets.
Several approaches such as in vitro selection (evolution) strategies (Orgel, 1979, Proc. R. Soc. London, B 205, 435) have been used to evolve new nucleic acid catalysts capable of catalyzing a variety of reactions, such as cleavage and ligation of phosphodiester linkages and amide linkages, (Joyce, 1989, Gene, 82, 83-87; Beaudry et al., 1992, Science 257, 635-641; Joyce, 1992, Scientific American 267, 90-97; Breaker et al, 1994, TIBTECH 12, 268; Bartel et al, 1993, Science 261:1411-1418; Szostak, 1993, TIBS 17, 89-93; Kumar et al, 1995, FASEB J., 9, 1183; Breaker, 1996, Curr. Op. Biotech., 1, 442). The development of ribozymes that are optimal for catalytic activity would contribute significantly to any strategy that employs RNA-cleaving ribozymes for the purpose of regulating gene expression. The hammerhead ribozyme, for example, functions with a catalytic rate (kcat) of about 1 min⁻¹in the presence of saturating (10 MM) concentrations of Mg²⁺ cofactor. An artificial “RNA ligase” ribozyme has been shown to catalyze the corresponding self-modification reaction with a rate of about 100 min⁻¹. In addition, it is known that certain modified hammerhead ribozymes that have substrate binding arms made of DNA catalyze RNA cleavage with multiple turn-over rates that approach 100 min⁻¹.
Making and Using Inhibitory Nucleic Acids
The nucleic acid sequences used to practice the methods described herein, whether RNA, cDNA, genomic DNA, vectors, viruses or hybrids thereof, can be isolated from a variety of sources, genetically engineered, amplified, and/or expressed/generated recombinantly. If desired, nucleic acid sequences of the invention can be inserted into delivery vectors and expressed from transcription units within the vectors. The recombinant vectors can be DNA plasmids or viral vectors. Generation of the vector construct can be accomplished using any suitable genetic engineering techniques well known in the art, including, without limitation, the standard techniques of PCR, oligonucleotide synthesis, restriction endonuclease digestion, ligation, transformation, plasmid purification, and DNA sequencing, for example as described in Sambrook et al. Molecular Cloning: A Laboratory Manual. (1989)), Coffin et al. (Retroviruses. (1997)) and “RNA Viruses: A Practical Approach” (Alan J. Cann, Ed., Oxford University Press, (2000)).
Preferably, inhibitory nucleic acids of the invention are synthesized chemically. Nucleic acid sequences used to practice this invention can be synthesized in vitro by well-known chemical synthesis techniques, as described in, e.g., Adams (1983) J. Am. Chem. Soc. 105:661; Belousov (1997) Nucleic Acids Res. 25:3440-3444; Frenkel (1995) Free Radic. Biol. Med. 19:373-380; Blommers (1994) Biochemistry 33:7886-7896; Narang (1979) Meth. Enzymol. 68:90; Brown (1979) Meth. Enzymol. 68:109; Beaucage (1981) Tetra. Lett. 22:1859; U.S. Pat. No. 4,458,066; WO/2008/043753 and WO/2008/049085, and the references cited therein.
Nucleic acid sequences of the invention can be stabilized against nucleolytic degradation such as by the incorporation of a modification, e.g., a nucleotide modification. For example, nucleic acid sequences of the invention includes a phosphorothioate at least the first, second, or third internucleotide linkage at the 5′ or 3′ end of the nucleotide to sequence. As another example, the nucleic acid sequence can include a 2′-modified nucleotide, e.g., a 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), or 2′-O—N-methylacetamido (2′-O—NMA). As another example, the nucleic acid sequence can include at least one 2′-O-methyl-modified nucleotide, and in some embodiments, all of the nucleotides include a 2′-O-methyl modification. In some embodiments, the nucleic acids are “locked,” i.e., comprise nucleic acid analogues in which the ribose ring is “locked” by a methylene bridge connecting the 2′-O atom and the 4′-C atom (see, e.g., Kaupinnen et al., Drug Disc. Today 2(3):287-290 (2005); Koshkin et al., J. Am. Chem. Soc., 120(50):13252-13253 (1998)). For additional modifications see US 20100004320, US 20090298916, and US 20090143326.
It is understood that any of the modified chemistries or formats of inhibitory nucleic acids described herein can be combined with each other, and that one, two, three, four, five, or more different types of modifications can be included within the same molecule.
Techniques for the manipulation of nucleic acids used to practice this invention, such as, e.g., subcloning, labeling probes (e.g., random-primer labeling using Klenow polymerase, nick translation, amplification), sequencing, hybridization and the like are well described in the scientific and patent literature, see, e.g., Sambrook et al., Molecular Cloning; A Laboratory Manual 3d ed. (2001); Current Protocols in Molecular Biology, Ausubel et al., eds. (John Wiley & Sons, Inc., New York 2010); Kriegler, Gene Transfer and Expression: A Laboratory Manual (1990); Laboratory Techniques In Biochemistry And Molecular Biology: Hybridization With Nucleic Acid Probes, Part I. Theory and Nucleic Acid Preparation, Tijssen, ed. Elsevier, N.Y. (1993).
Pharmaceutical Compositions
The methods described herein can include the administration of pharmaceutical compositions and formulations comprising inhibitory nucleic acid sequences designed to target an RNA.
In some embodiments, the compositions are formulated with a pharmaceutically acceptable carrier. The pharmaceutical compositions and formulations can be administered parenterally, topically, orally or by local administration, such as by aerosol or transdermally. The pharmaceutical compositions can be formulated in any way and can be administered in a variety of unit dosage forms depending upon the condition or disease and the degree of illness, the general medical condition of each patient, the resulting preferred method of administration and the like. Details on techniques for formulation and administration of pharmaceuticals are well described in the scientific and patent literature, see, e.g., Remington: The Science and Practice of Pharmacy, 21st ed., 2005.
The inhibitory nucleic acids can be administered alone or as a component of a pharmaceutical formulation (composition). The compounds may be formulated for administration, in any convenient way for use in human or veterinary medicine. Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions.
Formulations of the compositions of the invention include those suitable for intradermal, inhalation, oral/nasal, topical, parenteral, rectal, and/or intravaginal administration. The formulations may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. The amount of active ingredient (e.g., nucleic acid sequences of this invention) which can be combined with a carrier material to produce a single dosage form will vary depending upon the host being treated, the particular mode of administration, e.g., intradermal or inhalation. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound which produces a therapeutic effect, e.g., an antigen specific T cell or humoral response.
Pharmaceutical formulations of this invention can be prepared according to any method known to the art for the manufacture of pharmaceuticals. Such drugs can contain sweetening agents, flavoring agents, coloring agents and preserving agents. A formulation can be admixtured with nontoxic pharmaceutically acceptable excipients which are suitable for manufacture. Formulations may comprise one or more diluents, emulsifiers, preservatives, buffers, excipients, etc. and may be provided in such forms as liquids, powders, emulsions, lyophilized powders, sprays, creams, lotions, controlled release formulations, tablets, pills, gels, on patches, in implants, etc.
Pharmaceutical formulations for oral administration can be formulated using pharmaceutically acceptable carriers well known in the art in appropriate and suitable dosages. Such carriers enable the pharmaceuticals to be formulated in unit dosage forms as tablets, pills, powder, dragees, capsules, liquids, lozenges, gels, syrups, slurries, suspensions, etc., suitable for ingestion by the patient. Pharmaceutical preparations for oral use can be formulated as a solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable additional compounds, if desired, to obtain tablets or dragee cores. Suitable solid excipients are carbohydrate or protein fillers include, e.g., sugars, including lactose, sucrose, mannitol, or sorbitol; starch from corn, wheat, rice, potato, or other plants; cellulose such as methyl cellulose, hydroxypropylmethyl-cellulose, or sodium carboxy-methylcellulose; and gums including arabic and tragacanth; and proteins, e.g., gelatin and collagen. Disintegrating or solubilizing agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, alginic acid, or a salt thereof, such as sodium alginate. Push-fit capsules can contain active agents mixed with a filler or binders such as lactose or starches, lubricants such as talc or magnesium stearate, and, optionally, stabilizers. In soft capsules, the active agents can be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycol with or without stabilizers.
Aqueous suspensions can contain an active agent (e.g., nucleic acid sequences of the invention) in admixture with excipients suitable for the manufacture of aqueous suspensions, e.g., for aqueous intradermal injections. Such excipients include a suspending agent, such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia, and dispersing or wetting agents such as a naturally occurring phosphatide (e.g., lecithin), a condensation product of an alkylene oxide with a fatty acid (e.g., polyoxyethylene stearate), a condensation product of ethylene oxide with a long chain aliphatic alcohol (e.g., heptadecaethylene oxycetanol), a condensation product of ethylene oxide with a partial ester derived from a fatty acid and a hexitol (e.g., polyoxyethylene sorbitol mono-oleate), or a condensation product of ethylene oxide with a partial ester derived from fatty acid and a hexitol anhydride (e.g., polyoxyethylene sorbitan mono-oleate). The aqueous suspension can also contain one or more preservatives such as ethyl or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents and one or more sweetening agents, such as sucrose, aspartame or saccharin. Formulations can be adjusted for osmolarity.
In some embodiments, oil-based pharmaceuticals are used for administration of nucleic acid sequences of the invention. Oil-based suspensions can be formulated by suspending an active agent in a vegetable oil, such as arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin; or a mixture of these. See e.g., U.S. Pat. No. 5,716,928 describing using essential oils or essential oil components for increasing bioavailability and reducing inter- and intra-individual variability of orally administered hydrophobic pharmaceutical compounds (see also U.S. Pat. No. 5,858,401). The oil suspensions can contain a thickening agent, such as beeswax, hard paraffin or cetyl alcohol. Sweetening agents can be added to provide a palatable oral preparation, such as glycerol, sorbitol or sucrose. These formulations can be preserved by the addition of an antioxidant such as ascorbic acid. As an example of an injectable oil vehicle, see Minto (1997) J. Pharmacol. Exp. Ther. 281:93-102.
Pharmaceutical formulations can also be in the form of oil-in-water emulsions. The oily phase can be a vegetable oil or a mineral oil, described above, or a mixture of these. Suitable emulsifying agents include naturally-occurring gums, such as gum acacia and gum tragacanth, naturally occurring phosphatides, such as soybean lecithin, esters or partial esters derived from fatty acids and hexitol anhydrides, such as sorbitan mono-oleate, and condensation products of these partial esters with ethylene oxide, such as polyoxyethylene sorbitan mono-oleate. The emulsion can also contain sweetening agents and flavoring agents, as in the formulation of syrups and elixirs. Such formulations can also contain a demulcent, a preservative, or a coloring agent. In alternative embodiments, these injectable oil-in-water emulsions of the invention comprise a paraffin oil, a sorbitan monooleate, an ethoxylated sorbitan monooleate and/or an ethoxylated sorbitan trioleate.
The pharmaceutical compounds can also be administered by in intranasal, intraocular and intravaginal routes including suppositories, insufflation, powders and aerosol formulations (for examples of steroid inhalants, see e.g., Rohatagi (1995) J. Clin. Pharmacol. 35:1187-1193; Tjwa (1995) Ann. Allergy Asthma Immunol. 75:107-111). Suppositories formulations can be prepared by mixing the drug with a suitable non-irritating excipient which is solid at ordinary temperatures but liquid at body temperatures and will therefore melt in the body to release the drug. Such materials are cocoa butter and polyethylene glycols.
In some embodiments, the pharmaceutical compounds can be delivered transdermally, by a topical route, formulated as applicator sticks, solutions, suspensions, emulsions, gels, creams, ointments, pastes, jellies, paints, powders, and aerosols.
In some embodiments, the pharmaceutical compounds can also be delivered as microspheres for slow release in the body. For example, microspheres can be administered via intradermal injection of drug which slowly release subcutaneously; see Rao (1995) J. Biomater Sci. Polym. Ed. 7:623-645; as biodegradable and injectable gel formulations, see, e.g., Gao (1995) Pharm. Res. 12:857-863 (1995); or, as microspheres for oral administration, see, e.g., Eyles (1997) J. Pharm. Pharmacol. 49:669-674.
In some embodiments, the pharmaceutical compounds can be parenterally administered, such as by intravenous (IV) administration or administration into a body cavity or lumen of an organ. These formulations can comprise a solution of active agent dissolved in a pharmaceutically acceptable carrier. Acceptable vehicles and solvents that can be employed are water and Ringer's solution, an isotonic sodium chloride. In addition, sterile fixed oils can be employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid can likewise be used in the preparation of injectables. These solutions are sterile and generally free of undesirable matter. These formulations may be sterilized by conventional, well known sterilization techniques. The formulations may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents, e.g., sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate and the like. The concentration of active agent in these formulations can vary widely, and will be selected primarily based on fluid volumes, viscosities, body weight, and the like, in accordance with the particular mode of administration selected and the patient's needs. For IV administration, the formulation can be a sterile injectable preparation, such as a sterile injectable aqueous or oleaginous suspension. This suspension can be formulated using those suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation can also be a suspension in a nontoxic parenterally-acceptable diluent or solvent, such as a solution of 1,3-butanediol. The administration can be by bolus or continuous infusion (e.g., substantially uninterrupted introduction into a blood vessel for a specified period of time).
In some embodiments, the pharmaceutical compounds and formulations can be lyophilized. Stable lyophilized formulations comprising an inhibitory nucleic acid can be made by lyophilizing a solution comprising a pharmaceutical of the invention and a bulking agent, e.g., mannitol, trehalose, raffinose, and sucrose or mixtures thereof. A process for preparing a stable lyophilized formulation can include lyophilizing a solution about 2.5 mg/mL protein, about 15 mg/mL sucrose, about 19 mg/mL NaCl, and a sodium citrate buffer having a pH greater than 5.5 but less than 6.5. See, e.g., U.S. 20040028670.
The compositions and formulations can be delivered by the use of liposomes. By using liposomes, particularly where the liposome surface carries ligands specific for target cells, or are otherwise preferentially directed to a specific organ, one can focus the delivery of the active agent into target cells in vivo. See, e.g., U.S. Pat. Nos. 6,063,400; 6,007,839; Al-Muhammed (1996) J. Microencapsul. 13:293-306; Chonn (1995) Curr. Opin. Biotechnol. 6:698-708; Ostro (1989) Am. J. Hosp. Pharm. 46:1576-1587. As used in the present invention, the term “liposome” means a vesicle composed of amphiphilic lipids arranged in a bilayer or bilayers. Liposomes are unilamellar or multilamellar vesicles that have a membrane formed from a lipophilic material and an aqueous interior that contains the composition to be delivered. Cationic liposomes are positively charged liposomes that are believed to interact with negatively charged DNA molecules to form a stable complex. Liposomes that are pH-sensitive or negatively-charged are believed to entrap DNA rather than complex with it. Both cationic and noncationic liposomes have been used to deliver DNA to cells.
Liposomes can also include “sterically stabilized” liposomes, i.e., liposomes comprising one or more specialized lipids. When incorporated into liposomes, these specialized lipids result in liposomes with enhanced circulation lifetimes relative to liposomes lacking such specialized lipids. Examples of sterically stabilized liposomes are those in which part of the vesicle-forming lipid portion of the liposome comprises one or more glycolipids or is derivatized with one or more hydrophilic polymers, such as a polyethylene glycol (PEG) moiety. Liposomes and their uses are further described in U.S. Pat. No. 6,287,860.
The formulations of the invention can be administered for prophylactic and/or therapeutic treatments. In some embodiments, for therapeutic applications, compositions are administered to a subject who is need of reduced triglyceride levels, or who is at risk of or has a disorder described herein, in an amount sufficient to cure, alleviate or partially arrest the clinical manifestations of the disorder or its complications; this can be called a therapeutically effective amount. For example, in some embodiments, pharmaceutical compositions of the invention are administered in an amount sufficient to decrease serum levels of triglycerides in the subject.
The amount of pharmaceutical composition adequate to accomplish this is a therapeutically effective dose. The dosage schedule and amounts effective for this use, i.e., the dosing regimen, will depend upon a variety of factors, including the stage of the disease or condition, the severity of the disease or condition, the general state of the patient's health, the patient's physical status, age and the like. In calculating the dosage regimen for a patient, the mode of administration also is taken into consideration.
The dosage regimen also takes into consideration pharmacokinetics parameters well known in the art, i.e., the active agents' rate of absorption, bioavailability, metabolism, clearance, and the like (see, e.g., Hidalgo-Aragones (1996) J. Steroid Biochem. Mol. Biol. 58:611-617; Groning (1996) Pharmazie 51:337-341; Fotherby (1996) Contraception 54:59-69; Johnson (1995) J. Pharm. Sci. 84:1144-1146; Rohatagi (1995) Pharmazie 50:610-613; Brophy (1983) Eur. J. Clin. Pharmacol. 24:103-108; Remington: The Science and Practice of Pharmacy, 21st ed., 2005). The state of the art allows the clinician to determine the dosage regimen for each individual patient, active agent and disease or condition treated. Guidelines provided for similar compositions used as pharmaceuticals can be used as guidance to determine the dosage regiment, i.e., dose schedule and dosage levels, administered practicing the methods of the invention are correct and appropriate.
Single or multiple administrations of formulations can be given depending on for example: the dosage and frequency as required and tolerated by the patient, the degree and amount of therapeutic effect generated after each administration (e.g., effect on tumor size or growth), and the like. The formulations should provide a sufficient quantity of active agent to effectively treat, prevent or ameliorate conditions, diseases or symptoms.
In alternative embodiments, pharmaceutical formulations for oral administration are in a daily amount of between about 1 to 100 or more mg per kilogram of body weight per day. Lower dosages can be used, in contrast to administration orally, into the blood stream, into a body cavity or into a lumen of an organ. Substantially higher dosages can be used in topical or oral administration or administering by powders, spray or inhalation. Actual methods for preparing parenterally or non-parenterally administrable formulations will be known or apparent to those skilled in the art and are described in more detail in such publications as Remington: The Science and Practice of Pharmacy, 21st ed., 2005.
Various studies have reported successful mammalian dosing using complementary nucleic acid sequences. For example, Esau C., et al., (2006) Cell Metabolism, 3(2):87-98 reported dosing of normal mice with intraperitoneal doses of miR-122 antisense oligonucleotide ranging from 12.5 to 75 mg/kg twice weekly for 4 weeks. The mice appeared healthy and normal at the end of treatment, with no loss of body weight or reduced food intake. Plasma transaminase levels were in the normal range (AST ¾ 45, ALT ¾ 35) for all doses with the exception of the 75 mg/kg dose of miR-122 ASO, which showed a very mild increase in ALT and AST levels. They concluded that 50 mg/kg was an effective, non-toxic dose. Another study by Krützfeldt J., et al., (2005) Nature 438, 685-689, injected anatgomirs to silence miR-122 in mice using a total dose of 80, 160 or 240 mg per kg body weight. The highest dose resulted in a complete loss of miR-122 signal. In yet another study, locked nucleic acid molecules (“LNA molecules”) were successfully applied in primates to silence miR-122. Elmen J., et al., (2008) Nature 452, 896-899, report that efficient silencing of miR-122 was achieved in primates by three doses of 10 mg kg-1 LNA-antimiR, leading to a long-lasting and reversible decrease in total plasma cholesterol without any evidence for LNA-associated toxicities or histopathological changes in the study animals.
In some embodiments, the methods described herein can include co-administration with other drugs or pharmaceuticals, e.g., compositions for providing cholesterol homeostasis. For example, the inhibitory nucleic acids can be co-administered with drugs for treating or reducing risk of a disorder described herein.

EXAMPLES

The invention is further described in the following examples, which do not limit the scope of the invention described in the claims.

Example 1. A Denaturing CLIP-Seq Method for Identifying RNA Interactomes of Chromatin Complexes with High Specificity

PRC1 is Polycomb Repressive Complex 1, a Polycomb complex that is biochemically distinct from PRC2. PRC1 is the ezymatic complex that ubiquitylates histone H2A at lysine 119 (H2AK119Ub). Action of PRC1 on chromatin results in chromatin compaction and transcriptional repression. Although PRC1 binds thousands of sites in the mammalian genome, how PRC1 is targeted to chromatin has remained a mystery. YY1 may recruit PRC1 in some contexts, but is unlikely to be the general mechanism. RNA-mediated targeting is another potential mechanism. PRC1 is known to interact with at least one RNA—ANRIL (Yap et al., Mol Cell. 2010 Jun. 11; 38(5):662-74). This example describes methods that were developed to determing how many RNAs interact with PRC1 and whether they are a general recruiting tool for PRC1.
These “denaturing” CLIP-seq methods (also referred to herein as dCLIP-seq) utilize a biotin tag to enable purification of RNA-protein complexes under denaturing conditions to increase the specificity of the purification scheme. As shown in FIGS. 1A-B, for the to denaturing CLIP method, cell lines stably expressing two vectors were prepared: vector #1-expressing bacterial biotin ligase BirA under neomycin resistance; and vector #2—expressing a protein of interest (here, PRC1) fused to a biotinylation tag or control vector under puromycin resistance. Both human HEK 293 kidney cells and mouse 16.7 ES cells were used. Cells were crosslinked by exposure to ultraviolet (UV) light (254 nm) at 150-400 mJ/cm²on ice depending on cell layer thickness, cellular lysates are prepared, then treated with DNAse to solubilize the chromatin, and protein-RNA complexes were pulled down using streptavidin beads. Importantly, the samples were then washed with a high stringency wash using 8 M urea+0.1% SDS (range: 0.0-2.0%) at room temperature. Samples were then further washed in PBS+2% SDS and further in high salt buffer (PBS+750 mM NaCl+1% NP40+0.5% NaDeoxycholate+0.1% SDS), each at room temperature. Under such stringent conditions, most proteins are denatured, resulting in the loss of the nonspecific RNA-protein interactions. Only the extremely high-affinity biotin-avidin interaction survives. Thus, these steps can be used to effectively remove the vast majority of background RNA, resulting in extremely clean “peaks” of binding. The samples are then treated with DNAse to remove contaminating DNA. The RNA was phosphorylated using ³²P-ATP and run on SDS-PAGE and transferred onto a membrane. Broad bands corresponding to the RNA-PRC1 complex were identified by the presence of radioactive labeling (hot smear on the membrane) and then excised and eluted for cDNA preparation preparation prior to deep sequencing.
Peaks (high-frequency sequences, believed to correlate with protein binding sites on the RNA), were called by the following methods. About 40 million paired-end 50 nucleotide (nt) reads were generated for every dCLIP-seq sample. Adaptor sequences were trimmed with either Trim Galore! v0.3.3 (for dCLIP-seq; stringency 15 and allowed error rate 0.2), or cutadapt (v1.0). Identical sequences (PCR duplicates) were removed by custom programs prior to alignment. To account for the M. mus (mus)/M. castaneus (cas) hybrid character of mouse 16.7 ES cell line used for a dCLIP-seq, reads were first aligned to custom mus/129 and cas genomes, and then mapped back to the reference mm9 genome (Pinter et al., Genome Res 22, 1864-1876, 2012). For dCLIP-seq data obtained from human HEK293 cell line, alignments were performed to hg19 human reference genome. All alignments were performed with Tophat (v2.0.11) (Kim et al., Genome Biol 14, R36, 2013). Post-processing of alignments was performed with custom scripts using SAMtools (Li et al., Bioinformatics 25, 2078-2079, 2009), and BEDtools v2.17.0 (Quinlan and Hall, Bioinformatics 26, 841-842, 2010). These included accounting, alignment file-type conversion, extracting and sorting reads (SAMtools), and obtaining wig coverage files (SAMtools depth).
Fragment per million (fpm) wig files were then created by scaling uniquely aligned wig files to total number of fragments per million in each library (determined by SAMtools flagstat combining reads “with itself and mate mapped” and “singletons”). Then consecutive wig entries of equal coverage were merged forming bed files that were used for peak calling. The peak caller software peakranger (v. 16) (Uren et al., Bioinformatics 28, 3013-3020, 2012) was used. The software peakranger requires an even distribution of watson/crick entries, so prior to calling, strand specific bed file entries were randomized for strand. The software peakranger was called with arguments ranger −p 0.01—format bed—gene_annot_file (either mm9 or hg19 appropriate), −d experiment and −c mock-transfected control, to find narrow peaks with p-value 0.01 or less. To extract more uniquely aligned reads, a second round of peak calling was performed from the mus track, this time including “pegged” reads attained using tophat2 with the option −g 100. Pegged reads are singletons extracted from the reps track where the locus of one end is fixed locus and other varies. We then merged the results with the previous method.

Example 2. Human CBX7-RNA Binding Sites as Determined by Denaturing CLIP-Seq Analysis in Human 293 Cells

CLIP-seq performed in human female embryonic kidney fibroblast line, HEK293, as described above in Example 1. CBX7 binding sites in the RNA are shown in Table 1. Peaks were called from uniquely mapped reads using the software peakranger (p=0.01). The resulting strand specific bed files were then converted to their respective strands. To produce non-overlapping peaks, entries, from two biological replicate bed files were expanded by 500 nucleotides on each side and merged. The envelope of 500 bases was added because RNA-protein interactions could be affected by changes in nucleic acid folding nearby, which in turn could cause allosteric effects on the RNA-protein interaction. Then the closest gene was determined for each entry (bedtools closest) and categorized as “Imprinted” gene, “Oncogene”, and/or “Tumor Suppressor”.
Our analysis turned up 5893 binding sites in RNA for human CBX7. The columns (c) in Table 1 correspond to: c1, SEQ ID Number. c2, Chromosome number. c3, Read start position. c4, Read end position. c5, chromosome strand that the transcript is made from (+, top or Watson strand; −, bottom or Crick strand of each chromosome). C₆, nearest gene name. c7, gene categories as defined in the following way.
The hexadecimal code is used in Table 1 to indicate the number of categories satisfied by each gene: The 4 bit represents an Imprinted gene (IM). The 2 bit represents an Oncogene (OC). The 1 bit represents a Tumor Suppressor (TS). The hexadecimal code can be translated to binary. Each bit represents the condition (1) or absence (0) of the condition.
Thus:


Value	binary	meaning

0x1
0 0 1	TS
0x2
0 1 0	OC
0x3
0 1 1	TS and OC
0x4
1 0 0	IM
0x5
1 0 1	IM and TS
0x6
1 1 0	IM and OC
0x7
1 1 1	IM and OC and TS

Example 3. Mouse CBX7-RNA Binding Sites as Determined by Denaturing CLIP-Seq Analysis in ES Cells Derived from Mus musculus

CLIP-seq was performed as described in Example 1 in the mouse ES cell line, EL 16.7. CBX7 binding sites in the RNA are shown in Table 3. Peaks were called from uniquely mapped reads using the software peakranger (p=0.01). The resulting strand specific bed files were then converted to their respective strand. To produce non-overlapping peaks entries, 3 biological replicates of undifferentiated and 1 biological replicate of day 7-differentiated ES cells were expanded by 500 nucleotides on each side and merged. The envelope of 500 bases was added because RNA-protein interactions could be affected by changes in nucleic acid folding nearby, which in turn could cause allosteric effects on the RNA-protein interaction. Then the closest gene was determined for each entry (bedtools closest) and categorized as “Imprinted” gene, “Oncogene”, and/or “Tumor Suppressor”.
Our analysis revealed 18,953 binding sites (peaks) in RNA for mouse ES cells. The columns (c) in Table 3 correspond to: c1, SEQ ID Number. c2, Chromosome number. c3, Read start position. c4, Read end position. c5, chromosome strand that the transcript is made from (+, top or Watson strand; −, bottom or Crick strand of each chromosome). C6, nearest gene name. c7, gene categories as defined above in Example 2.

Example 4. Human LiftOver Sequences Corresponding to CBX7-RNA Binding Sites as Determined by Denaturing CLIP-Seq Analysis in Mouse ES Cells

CBX7-binding sites shown in Table 2 were derived from dCLIP-seq performed in the mouse ES cell line, 16.7, as shown in Table 3, translated from mouse mm9 to human hg19 coordinates. The software UCSC Liftover was used to convert mouse mm9 coordinates from the mouse sub-sheet to human hg19 in the human liftover sub-sheet, prior to the envelope extension and merge step. The analysis led to 11,522 binding sites in human RNA. The columns (c) in Table 2 correspond to: c1, SEQ ID Number. c2, Chromosome number. c3, Read start position. c4, Read end position. c5, chromosome strand that the transcript is made from (+, top or Watson strand; −, bottom or Crick strand of each chromosome). C6, nearest gene name. c7, gene categories as defined in Example 2.

Example 5. Targeting the PRC1-RNA Interaction to Modulate Gene Expression

Analysis of the results described above indicated that PRC1 binding sites can be classified into several groups, including (i) 3′ untranslated region [3′ UTR], (ii) promoter-associated, (iii) gene body, (iv) antisense, and (v) intergenic. In order to block the identified interactions between Cbx7 and specific RNA transcripts, antisense oligonucleotides (ASO) LNAs were administered to cells in culture, to determine whether targeting the interaction between PRC1 and each of these RNA classes would change gene expression in cis.
First, the effects of disrupting PRC1-3′UTR interactions were examined. Potential Cbx7 binding sites (identified as described above) that were within 3′UTRs of three selected transcripts were identified based on CLIP-seq data, including (FIG. 2A) Mouse DDB1 and CUL4 Associated Factor 12-Like 1 (Dcaf12L1); (FIG. 2B) Mouse Calmodulin 2 (Calm2); (FIG. 2C) Mouse Mecp2; and Human IRAK1. 22-mer mixmer LNAs targeting selected binding sites (FIG. 3 ) were designed with the following sequences:

TABLE 4

Sequences of LNAs targeting Dusp9,
Dcaf12L1, IRAK1, Mecp2, and Calm2

Target		LNA	SEQ ID
Gene	LNA I.D	sequence	NO:

Dusp9	Dusp9-1-	CCTACAGTTCC	36372
	a	AAGAAGTCTAA

	Dusp9-1-	GAAGCAGGAAG	36373
	b	GAGTCTACACG

	Dusp9-2-	CAGTTTGACCA	36374
	a	CCCTCAGTCAC

	Dusp9-2-	AAAGAAACAGT	36375
	b	CAGGGCACCAG

	Dusp9-3-	CACAGGTATTG	36376
	a	CCAGCTCCAGG

	Dusp9-3-	CACACACACAG	36377
	b	AGTCTACAACG

Dcaf12L1	Dcaf12L1-	CCTGTCTGCCA	36378
	1	TACATTCTACA

	Dcaf12L1-	GCTCAGACTTC	36379
	2	TTCCTTTGCAC

	Dcaf12L1-	GTAACAGATCT	36380
	3	ATTCTACTTGA

	Dcaf12L1-	CATTATCTCTA	36381
	4-a	TTTATCTGAAC

	Dcaf12L1-	GGAGAAAACCA	36382
	4-b	ATCTATCCGCA

Calm2	Calm2-1-	GCCAGAGTAAG	36383
	a	CCACATGCAAC

	Calm2-1-	TTAGATGTGCA	36384
	b	GACGGGCTTAG

	Calm2-2-	TTACAGCTCCA	36385
	a	CACTTCAACAA
		C

	Calm2-2-	ACATGCTGACA	36386
	b	GTTCCTAAAAG

Scrambled	LNA-Scr	GTGTAACACGT	36387
control		CTATACGCCCA

Tsix	Tsix-	AGAGTACAGTT	36388
	region-1	AACAAGCTGGG
		T

	Tsix-	TGTTTTGTGAC	36389
	region-2	AGGGATTCT

	Tsix-	TTCTTCCTTGC	36390
	region-	ATTGTGTCTA
	3a

	Tsix-	GGTGTGTCCTA	36391
	region-	TGGTCCTATGT
	3b

	Tsix-	CCATGTAACAG	36392
	region-	AATGTTGAGAT
	3c

	Tsix-	CATAATCTGTG	36393
	region-	ACCAGTACCTC
	4a

	Tsix-	CATCAGAAGAG	36394
	region-	GTTAGATAT
	4b

	Tsix-	TGGAGGCAGGT	36395
	region-	GGATTTCTAAC
	4c

IRAK1	IRAK1-a	CCAACATGCGC	36396
		CAGCCTCCTCA

	IRAK1-b	AAGTGCTGGGA	36397
		TTACAGGCGTG

	IRAK1-c	ATCATGACTCA	36398
		CTGCAGCCTCG

Mecp2	Mecp2-	TCGCTATACCA	36399
	reg1-a	CAGTCCACAGG

	Mecp2-	TGAAGCAGAGA	36400
	reg1-b	GCAGGAAGAAG

	Mecp2-	ACACCTCAAAT	36401
	reg1-c	CTCAAGAGGCT

	Mecp2-	GATTACTCCCT	36402
	reg2-a	AGAGCAAGGCC

	Mecp2-	CACAAGGAAAG	36403
	reg2-b	GGCTCGGCACA

	Mecp2-	CCACTTCCCTC	36404
	reg2-c	CCTTCAAATGC

Phosphate residues were replaced with phosphorothioate residues for increased stability. Multiple LNA oligonucleotides (LNAs) targeting the same transcript were pooled together to the final concentration of 50 μM. Following trypsinization and feeder removal, a total of 2×10⁶EL16.7 mouse ES cells were resuspended in 100 μM of ES cell nucleofector solution (Lonza) supplemented with 2 μM LNAs. The cells were transfected using the A-030 program. A 0.5 mL of culture medium was added to the cells and 250 μL of this suspension was plated on gelatinized 6-well tissue culture dish with 2 ml of fibroblast-conditioned media. Per time point, whole cell RNA was extracted using a Trizol reagent and expression of the target genes was estimated using quantitative real-time RT-PCR (normalized to beta-actin as a reference gene).
The effect of LNAs on gene expression was represented as a ratio between specific LNAs and scrambled control. The results are shown in FIGS. 3 and 5A-B. To test the specificity of LNA pools, two unrelated amplicons were tested for every LNA pool along with a specific one. There was a specific increase in Dcaf12L1 gene expression 24 hrs after nucleofection with the Dcaf12L1-specific LNA pool as compared to unrelated Calm2 or to Dusp9 genes (FIG. 3 , right). The same was true for the LNA pool against Calm2, which resulted in a specific increase in Calm2 mRNA levels as compared to unrelated Dsup9 and Dcaf12L1 genes 24 hrs after nucleofection (FIG. 3 , left). These results indicate that targeting the RNA interaction with PRC1 lead to an increase in gene expression.
In contrast, LNAs targeting Mecp2 and IRAK1 interaction with PRC1-binding RNA resulted in gene downregulation, presumably as a result of disrupting PRC1 RNA interactions. Mouse embryonic fibroblasts (MEFs) were nucleofected with pooled LNAs and harvested after 24 hours for qRT-PCR analysis of Mecp2 expression. Downregulation was seen after Mecp2-specific LNA treatment, but not seen with LNAs against Tsix or scrambled control. In addition, human PC3 cells were transfected with pooled IRAK1-specific LNA or control scrambled LNA, then harvested after 24 hours or 36 hours for qRT-PCR analysis of IRAK1 expression. Specific downregulation was seen for IRAK1-specific LNA. Thus, these LNAs caused downregulation but not elimination of gene expression in cis. Thus, targeting 3′ UTR-PRC1 interactions by antisense oligonucleotides provides an alternative approach to RNAi methods and may be especially useful when one aims to titrate down but not eliminate gene expression, such as in the case of MECP 2 Duplication Syndrome.
Second, we examined the effects of disrupting PRC1-antisense RNA interactions. As an example, Tsix RNA is antisense to Xist and binds PRC1 via CBX7 at both Tsix's 5′ and 3′ ends. Tsix RNA is a known repressor ofXist expression but the mechanisms of repression have not be fully elucidated. Here we hypothesized that Tsix in part recruits PRC1 to repress Xist expression. Targeting Tsix RNA with ASO mixmers led to increased Xist expression even after just 6 hours of treatment (FIG. 4A,B), consistent with a derepression of Xist when PRC1 cannot be recruited. Furthermore, ANRIL is antisense to INK4a and interacts with CBX7. Targeting ANRIL is expected to lead to derepression of the linked coding gene INK4a, consistent with loss of ANRIL-PRC1 interactions. Thus, antisense RNAs interact with PRC1 and serve as recruiting tools for PRC1 in cis.
Third, we examined the effects of disrupting PRC1-intergenic RNA interactions. Genes can either be turned up or down. For example, Xist is a CBX7 target. Xist recruits PRC1 via CBX7 to the rest of the X-chromosome. Targeting Xist binding sites is expected to prevent PRC1 recruitment and leads to failure of X-inactivation or higher likelihood of X-reactivation. As an opposite example, Pvt1 is a long noncoding RNA located next to c-Myc and is a frequent site of translocations in B-cell lymphomas (e.g., Burkitt's). Pvt1 and to cMyc are both associated with oncogenesis. Pvt1 appears to be a positive regulator of cMyc expression. Our analysis shows that Pvt1 is a PRC1 target. Pvt1 may recruit PRC1 and result in upregulation of cMyc.
These data indicate that PRC1-RNA interactions may serve different functions within cells and genes may be up- or down-regulated by disrupting these CBX7-RNA interactions.

1	chr1	840144	841315	+	SAMD11	0x0
2	chr1	852326	853425	−	LOC100130417	0x0
3	chr1	864967	866163	+	SAMD11	0x0
4	chr1	879290	880468	−	NOC2L	0x0
5	chr1	893660	894797	−	NOC2L	0x0
6	chr1	933795	934971	−	HES4	0x0
7	chr1	939820	940963	+	ISG15	0x1
8	chr1	941875	943019	+	ISG15	0x1
9	chr1	990208	992002	+	AGRN	0x0
10	chr1	1018302	1019453	−	C1orf159	0x0
11	chr1	1042955	1044169	−	C1orf159	0x0
12	chr1	1155610	1156790	−	SDF4	0x0
13	chr1	1221945	1223142	+	SCNN1D	0x0
14	chr1	1240971	1242078	−	ACAP3	0x0
15	chr1	1244270	1245370	−	ACAP3	0x0
16	chr1	1244824	1245997	−	PUSL1	0x0
17	chr1	1250751	1251923	−	CPSF3L	0x0
18	chr1	1253901	1255113	−	CPSF3L	0x0
19	chr1	1257950	1259068	−	CPSF3L	0x0
20	chr1	1270872	1272024	−	DVL1	0x4
21	chr1	1287069	1288262	+	TAS1R3	0x0
22	chr1	1327280	1328568	−	CCNL2	0x0
23	chr1	1482465	1483678	−	SSU72	0x0
24	chr1	1497825	1498974	−	SSU72	0x0
25	chr1	1499242	1500446	−	SSU72	0x0
26	chr1	1531126	1532227	−	C1orf233	0x0
27	chr1	1534005	1535150	−	C1orf233	0x0
28	chr1	1554365	1555575	+	MIB2	0x0
29	chr1	1717245	1718531	−	GNB1	0x0
30	chr1	2087331	2088452	+	PRKCZ	0x0
31	chr1	2186545	2187672	+	SKI	0x0
32	chr1	2258187	2259377	−	MORN1	0x0
33	chr1	2970525	2971680	−	FU42875	0x0
34	chr1	3696643	3697775	−	LRRC47	0x0
35	chr1	3712359	3713583	−	LRRC47	0x0
36	chr1	5221620	5222816	+	AJAP1	0x0
37	chr1	6244753	6246027	−	RPL22	0x6
38	chr1	6257275	6258424	−	RPL22	0x6
39	chr1	6283411	6284533	−	ICMT	0x0
40	chr1	6438381	6439534	−	ACOT7	0x0
41	chr1	6584050	6585244	−	NOL9	0x0
42	chr1	6605037	6606171	−	NOL9	0x0
43	chr1	6651267	6652348	−	KLHL21	0x0
44	chr1	6695045	6696146	−	DNAJC11	0x1
45	chr1	6709976	6711146	−	DNAJC11	0x1
46	chr1	6844973	6846190	+	CAMTA1	0x1
47	chr1	8387551	8388748	+	SLC45A1	0x0
48	chr1	8411950	8413097	−	RERE	0x0
49	chr1	8556917	8558157	−	RERE	0x0
50	chr1	8667679	8668827	−	RERE	0x0
51	chr1	8922743	8923838	−	ENO1	0x0
52	chr1	8924945	8926044	−	ENO1	0x0
53	chr1	8926640	8927823	−	ENO1	0x0
54	chr1	9364627	9365824	+	SPSB1	0x0
55	chr1	9648465	9649637	+	TMEM201	0x0
56	chr1	9797015	9798190	−	CLSTN1	0x0
57	chr1	10006837	10008034	+	NMNAT1	0x0
58	chr1	10210619	10211845	+	UBE4B	0x1
59	chr1	10212128	10213323	+	UBE4B	0x1
60	chr1	10219898	10221032	+	UBE4B	0x1
61	chr1	10437072	10438185	+	KIF1B	0x1
62	chr1	10517254	10518437	−	DFFA	0x0
63	chr1	10519910	10521155	−	DFFA	0x0
64	chr1	11082896	11084096	+	TARDBP	0x0
65	chr1	11086612	11087712	+	TARDBP	0x0
66	chr1	11114167	11115339	−	SRM	0x0
67	chr1	11166821	11168000	−	MTOR	0x0
68	chr1	11190033	11191197	−	MTOR	0x0
69	chr1	11845848	11847032	−	MTHFR	0x0
70	chr1	11967643	11968911	+	PLOD1	0x0
71	chr1	11969319	11970555	−	KIAA2013	0x0
72	chr1	12024759	12025894	+	PLOD1	0x0
73	chr1	12071654	12072919	+	MFN2	0x0
74	chr1	12081168	12082397	+	MIIP	0x0
75	chr1	12337286	12338484	+	VPS13D	0x0
76	chr1	12496061	12497240	−	DHRS3	0x0
77	chr1	12534409	12535606	+	VPS13D	0x0
78	chr1	12828806	12829927	+	PRAMEF12	0x0
79	chr1	15931136	15932327	+	DDI2	0x0
80	chr1	16046315	16047483	+	PLEKHM2	0x0
81	chr1	16158644	16159843	−	FU37453	0x0
82	chr1	16163602	16164745	+	SPEN	0x0
83	chr1	16176405	16177587	+	SPEN	0x0
84	chr1	16198975	16200210	+	SPEN	0x0
85	chr1	16202208	16203403	+	SPEN	0x0
86	chr1	16256261	16257458	+	SPEN	0x0
87	chr1	16263796	16264969	+	SPEN	0x0
88	chr1	16265815	16266883	+	SPEN	0x0
89	chr1	16780855	16781964	−	CROCCP3	0x0
90	chr1	16846525	16847742	−	CROCCP3	0x0
91	chr1	16871860	16873033	−	NBPF1	0x0
92	chr1	17004176	17005430	−	ESPNP	0x0
93	chr1	17053194	17054426	+	MIR3675	0x0
94	chr1	17186168	17187363	+	CROCC	0x2
95	chr1	17187862	17189092	+	CROCC	0x2
96	chr1	17733274	17734587	−	RCC2	0x0
97	chr1	17748766	17749972	−	RCC2	0x0
98	chr1	19207589	19208765	−	ALDH4A1	0x0
99	chr1	19407485	19408666	−	UBR4	0x0
100	chr1	19467661	19468839	−	UBR4	0x0
101	chr1	19480827	19482021	−	UBR4	0x0
102	chr1	19510062	19511162	−	UBR4	0x0
103	chr1	19518563	19519634	−	UBR4	0x0
104	chr1	19625557	19627771	−	AKR7A2	0x0
105	chr1	19934145	19935669	+	C1orf151-NBL1	0x0
106	chr1	19934145	19935669	+	MINOS1	0x0
107	chr1	21068879	21070073	−	HP1BP3	0x0
108	chr1	21101451	21102605	−	HP1BP3	0x0
109	chr1	21112219	21113345	−	HP1BP3	0x0
110	chr1	21180924	21182129	−	EIF4G3	0x0
111	chr1	21219529	21220598	−	EIF4G3	0x0
112	chr1	21357497	21358722	−	EIF4G3	0x0
113	chr1	21368009	21369192	−	EIF4G3	0x0
114	chr1	21469103	21470320	−	EIF4G3	0x0
115	chr1	21483420	21484575	−	EIF4G3	0x0
116	chr1	21499884	21501032	−	EIF4G3	0x0
117	chr1	22022042	22023220	−	USP48	0x0
118	chr1	22090919	22092045	−	USP48	0x0
119	chr1	22175614	22176789	−	H5PG2	0x0
120	chr1	22418197	22419329	+	CDC42	0x2
121	chr1	22438373	22439541	+	CDC42	0x2
122	chr1	23604893	23606066	−	HNRNPR	0x0
123	chr1	23611267	23612409	−	HNRNPR	0x0
124	chr1	23636297	23637464	−	HNRNPR	0x0
125	chr1	23664466	23665686	−	HNRNPR	0x0
126	chr1	23696173	23697372	+	C1orf213	0x0
127	chr1	24018563	24019764	+	RPL11	0x0
128	chr1	24035667	24036809	+	RPL11	0x0
129	chr1	24053341	24054440	+	TCEB3	0x0
130	chr1	24055464	24056625	+	TCEB3	0x0
131	chr1	24086902	24088096	−	LOC100506963	0x0
132	chr1	24121383	24122585	+	LYPLA2	0x0
133	chr1	24321543	24322767	+	PNRC2	0x0
134	chr1	24795527	24796626	+	NIPAL3	0x0
135	chr1	25168610	25169758	+	CLIC4	0x0
136	chr1	25686991	25688242	+	TMEM50A	0x0
137	chr1	26142500	26144914	+	SEPN1	0x0
138	chr1	26226551	26228033	−	STMN1	0x0
139	chr1	26799856	26800971	+	HMGN2	0x0
140	chr1	27212259	27213402	−	GPN2	0x0
141	chr1	27435519	27436813	−	SLC9A1	0x0
142	chr1	27586882	27588101	+	WDTC1	0x0
143	chr1	27632491	27633959	+	WDTC1	0x0
144	chr1	27730967	27732179	−	WASF2	0x0
145	chr1	27732345	27740500	−	WASF2	0x0
146	chr1	28240102	28241240	−	RPA2	0x0
147	chr1	28298923	28300079	−	EYA3	0x0
148	chr1	28352695	28353858	−	EYA3	0x0
149	chr1	28833307	28835831	+	RCC1	0x0
150	chr1	28833307	28835831	+	SNHG3	0x0
151	chr1	28904692	28908087	−	SNHG12	0x0
152	chr1	28904692	28908087	−	SNORA16A	0x0
153	chr1	28904692	28908087	−	SNORA44	0x0
154	chr1	28904692	28908087	−	SNORA61	0x0
155	chr1	28904692	28908087	−	SNORD99	0x0
156	chr1	28974564	28975822	+	RNU11	0x0
157	chr1	29247305	29248543	+	EPB41	0x1
158	chr1	29308535	29309673	−	TMEM200B	0x0
159	chr1	29444554	29446232	+	EPB41	0x1
160	chr1	29474230	29475417	−	SRSF4	0x0
161	chr1	29480719	29481895	−	SRSF4	0x0
162	chr1	30305391	30306547	−	MECR	0x0
163	chr1	31316149	31317342	+	LOC100129196	0x0
164	chr1	31467449	31468593	−	PUM1	0x0
165	chr1	31478154	31479311	−	PUM1	0x0
166	chr1	32203368	32204547	−	BAI2	0x1
167	chr1	32228432	32229591	−	BAI2	0x1
168	chr1	32507902	32509306	+	KHDRBS1	0x0
169	chr1	32640327	32641537	+	KPNA6	0x0
170	chr1	32661663	32662812	+	TXLNA	0x0
171	chr1	32689077	32690271	+	EIF3I	0x0
172	chr1	32800031	32801234	−	MARCKSL1	0x0
173	chr1	33051782	33052957	−	ZBTB8A	0x0
174	chr1	33086866	33088028	−	Z8TB8OS	0x0
175	chr1	33474529	33475637	−	AK2	0x0
176	chr1	33765318	33766520	+	ZNF362	0x0
177	chr1	34029443	34030618	−	CSMD2	0x0
178	chr1	35316677	35317863	−	C1orf212	0x0
179	chr1	35648193	35650636	−	SFPQ	0x2
180	chr1	35651800	35652899	−	SFPQ	0x2
181	chr1	35656343	35657533	−	SFPQ	0x2
182	chr1	36031642	36032886	+	NCDN	0x0
183	chr1	36063797	36064965	−	PSMB2	0x0
184	chr1	36307953	36309152	+	EIF2C4	0x0
185	chr1	36388167	36389851	+	EIF2C1	0x0
186	chr1	36614384-	36615568	−	TRAPPC3	0x0
187	chr1	36807748	36808925	−	STK40	0x0
188	chr1	39469513	39470715	+	AKIRIN1	0x0
189	chr1	39493910	39495136	+	NDUFS5	0x0
190	chr1	40029630	40030729	−	PABPC4	0x0
191	chr1	40032527	40033665	−	PABPC4	0x0
192	chr1	40032527	40033665	−	SNORA55	0x0
193	chr1	40041718	40042871	−	PABPC4	0x0
194	chr1	40413156	40414381	+	MFSD2A	0x1
195	chr1	40428168	40429524	+	MFSD2A	0x1
196	chr1	40537396	40538555	+	CAP1	0x0
197	chr1	40537899	40539087	−	PPT1	0x0
198	chr1	40598294	40599496	+	RLF	0x0
199	chr1	40930541	40931733	+	ZNF643	0x0
200	chr1	41476871	41478119	+	CTPS	0x0
201	chr1	41608008	41609172	−	SCMH1	0x0
202	chr1	41919561	41920665	+	LOC100507178	0x0
203	chr1	42641695	42642843	−	FOXJ3	0x0
204	chr1	42643332	42644469	−	FOXJ3	0x0
205	chr1	43161880	43162989	+	YBX1	0x0
206	chr1	43167147	43168350	+	YBX1	0x0
207	chr1	44125402	44126640	+	KDM4A	0x0
208	chr1	44170298	44171502	+	KDM4A	0x0
209	chr1	44369888	44371081	+	ST3GAL3	0x0
210	chr1	44371265	44372436	+	ST3GAL3	0x0
211	chr1	44442659	44443906	+	ATP6V0B	0x0
212	chr1	44911247	44912431	+	RNF220	0x0
213	chr1	45062534	45063657	−	TMEM53	0x0
214	chr1	45186916	45188147	−	TMEM53	0x0
215	chr1	45196159	45197386	−	BEST4	0x0
216	chr1	45240987	45242949	+	RPS8	0x0
217	chr1	45240987	45242949	+	SNORD46	0x0
218	chr1	45240987	45242949	+	SNORD55	0x0
219	chr1	45242965	45244687	+	RPS8	0x0
220	chr1	45242965	45244687	+	SNORD38A	0x0
221	chr1	45242965	45244687	+	SNORD38B	0x0
222	chr1	45284993	45286220	−	PTCH2	0x1
223	chr1	46125981	46127259	−	GPBP1L1	0x0
224	chr1	46148262	46149412	−	GPBP1L1	0x0
225	chr1	46654276	46655502	−	POMGNT1	0x0
226	chr1	46859410	46860537	+	FAAH	0x0
227	chr1	47745459	47746710	−	STIL	0x0
228	chr1	47774668	47775846	−	STIL	0x0
229	chr1	49275861	49277039	−	BEND5	0x0
230	chr1	51049850	51051026	−	FAF1	0x0
231	chr1	51189287	51190509	−	FAF1	0x0
232	chr1	51715868	51717079	−	TTC39A	0x0
233	chr1	51787282	51788462	−	TTC39A	0x0
234	chr1	52379262	52380464	−	RAB3B	0x0
235	chr1	52438512	52439715	+	BTF3L4	0x0
236	chr1	52826661	52827803	−	CC2D1B	0x0
237	chr1	52837435	52838617	−	ORC1	0x2
238	chr1	53336515	53337624	+	ZYG11A	0x0
239	chr1	53349000	53350130	+	ZYG11A	0x0
240	chr1	53367018	53368216	+	ZYG11A	0x0
241	chr1	53491985	53493213	+	SCP2	0x0
242	chr1	53716288	53717467	−	LRP8	0x0
243	chr1	55315885	55317555	−	DHCR24	0x0
244	chr1	57129718	57130907	+	PRKAA2	0x0
245	chr1	59248014	59249266	−	JUN	0x2
246	chr1	60868316	60869493	+	HOOK1	0x0
247	chr1	61663674	61664848	+	NFIA	0x0
248	chr1	63182476	63183613	−	DOCK7	0x0
249	chr1	65008049	65009293	+	CACHD1	0x0
250	chr1	65234621	65235845	+	RAVER2	0x0
251	chr1	65523304	65524453	−	MIR101-1	0x1
252	chr1	65523304	65524453	−	MIR3671	0x0
253	chr1	67873676	67875700	−	SERBP1	0x0
254	chr1	67878205	67879389	−	SERBP1	0x0
255	chr1	67887368	67888559	−	SERBP1	0x0
256	chr1	68166950	68168313	−	GNG12	0x0
257	chr1	68273081	68274225	−	GNG12	0x0
258	chr1	70067427	70068625	+	LRRC7	0x0
259	chr1	70686727	70688033	+	SRSF11	0x2
260	chr1	76252214	76253404	+	RABGGTB	0x0
261	chr1	76252214	76253404	+	SNORD45C	0x0
262	chr1	77554193	77555417	−	PIGK	0x0
263	chr1	78170124	78171311	−	USP33	0x0
264	chr1	78410310	78411448	−	FUBP1	0x2
265	chr1	78434297	78435474	−	FUBP1	0x2
266	chr1	82403020	82404264	+	LPHN2	0x2
267	chr1	84570348	84571545	+	PRKACB	0x0
268	chr1	84966968	84968146	−	GNG5	0x0
269	chr1	85330676	85331965	−	LPAR3	0x0
270	chr1	85610552	85611775	−	SYDE2	0x0
271	chr1	86057408	86058620	+	CYR61	0x0
272	chr1	86079240	86080418	−	ZNHIT6	0x0
273	chr1	87426543	87427773	+	HS2ST1	0x0
274	chr1	87511146	87512431	+	HS2ST1	0x0
275	chr1	89255594	89256826	+	PKN2	0x0
276	chr1	89259619	89260755	+	PKN2	0x0
277	chr1	89270987	89272231	+	PKN2	0x0
278	chr1	90341079	90342295	+	LRRC8D	0x0
279	chr1	90472119	90473511	+	ZNF326	0x0
280	chr1	91363596	91364776	−	ZNF644	0x0
281	chr1	91852202	91853725	−	HFM1	0x0
282	chr1	92326566	92327783	−	TGFBR3	0x1
283	chr1	92724108	92725226	−	GLMN	0x0
284	chr1	92975994	92977194	−	EVI5	0x0
285	chr1	93588727	93590210	+	MTF2	0x0
286	chr1	93618375	93619763	−	TMED5	0x0
287	chr1	93803508	93804686	−	LOC100131564	0x0
288	chr1	93810953	93812167	+	DR1	0x0
289	chr1	94312549	94313776	+	MIR760	0x0
290	chr1	94899930	94901140	+	ABCD3	0x0
291	chr1	95401336	95402708	+	LOC729970	0x0
292	chr1	96690973	96692200	+	PTBP2	0x0
293	chr1	96911938	96913259	+	PTBP2	0x0
294	chr1	98628031	98629273	+	LOC729987	0x0
295	chr1	100139712	100140929	+	PALMD	0x0
296	chr1	100547299	100548483	+	HIAT1	0x0
297	chr1	101486719	101487914	−	DPH5	0x0
298	chr1	102251585	102252999	−	OLFM3	0x0
299	chr1	103507706	103508886	−	COL11A1	0x2
300	chr1	108112882	108114057	−	VAV3	0x0
301	chr1	109241985	109243695	+	PRPF38B	0x0
302	chr1	109604746	109605960	−	TAF13	0x0
303	chr1	109642240	109643797	+	SCARNA2	0x0
304	chr1	109852954	109854306	−	SORT1	0x0
305	chr1	110563994	110565230	+	AHCYL1	0x0
306	chr1	110881918	110883020	+	RBM15	0x2
307	chr1	110889786	110890938	+	RBM15	0x2
308	chr1	111983105	111984257	−	WDR77	0x0
309	chr1	112001663	112002811	+	ATP5F1	0x0
310	chr1	112186658	112187879	+	RAP1A	0x1
311	chr1	112198778	112199981	+	RAP1A	0x1
312	chr1	113212803	113214334	+	CAPZA1	0x0
313	chr1	113454053	113456912	−	SLC16A1	0x0
314	chr1	113459502	113460782	−	SLC16A1	0x0
315	chr1	113552218	113553398	+	LRIG2	0x0
316	chr1	113711026	113712272	+	LRIG2	0x0
317	chr1	114216414	114217630	+	MAGI3	0x0
318	chr1	115248058	115249362	−	NRAS	0x2
319	chr1	115259278	115261005	−	CSDE1	0x0
320	chr1	115259278	115261005	−	NRAS	0x2
321	chr1	115268298	115269476	−	CSDE1	0x0
322	chr1	115269811	115271040	+	SYCP1	0x0
323	chr1	115272477	115273735	−	CSDE1	0x0
324	chr1	115277451	115278611	−	CSDE1	0x0
325	chr1	116915330	116916732	+	ATP1A1	0x0
326	chr1	116926045	116927247	+	ATP1A1	0x0
327	chr1	116932313	116933518	+	ATP1A1	0x0
328	chr1	116946522	116947737	+	ATP1A1	0x0
329	chr1	117452059	117453257	+	PTGFRN	0x0
330	chr1	117640591	117641790	+	TTF2	0x0
331	chr1	117910253	117911401	+	MAN1A2	0x0
332	chr1	117944308	117945714	+	MAN1A2	0x0
333	chr1	117993522	117994752	+	MAN1A2	0x0
334	chr1	118530435	118531631	−	SPAG17	0x0
33S	chr1	120543418	120544633	−	NOTCH2	0x2
336	chr1	144055799	144057061	+	SRGAP2P2	0x0
337	chr1	144857432	144858775	−	PDE4DIP	0x2
338	chr1	144881054	144882227	−	PDE4DIP	0x2
339	chr1	144900376	144901530	−	PDE4DIP	0x2
340	chr1	144921748	144923136	−	PDE4DIP	0x2
341	chr1	145115870	145116991	+	SEC22B	0x0
312	chr1	145382265	145383487	+	NBPF10	0x0
343	chr1	145394939	145396145	−	POLR3GL	0x0
344	chr1	145508701	145509914	+	RBM8A	0x0
34S	chr1	145510390	145511633	+	RBM8A	0x0
346	chr1	145577621	145578843	+	PIAS3	0x0
347	chr1	146555618	146556791	−	LOC728989	0x0
348	chr1	147510499	147511710	−	PDZK1P1	0x0
349	chr1	147825129	147826328	+	GPR89C	0x0
350	chr1	147993651	147994895	+	GPR89C	0x0
351	chr1	148240938	148242186	+	NBPF15	0x0
352	chr1	148247512	148248779	+	NBPF15	0x0
353	chr1	148344173	148345590	−	PPIAL4D	0x0
354	chr1	148344173	148345590	−	PPIAL4F	0x0
355	chr1	149193532	149194786	−	HIST2H2BF	0x0
356	chr1	149223492	149224764	−	HIST2H2BF	0x0
357	chr1	149229993	149231191	−	HIST2H2BF	0x0
358	chr1	149294107	149295294	−	HIST2H2BF	0x0
359	chr1	149298025	149299210	−	HIST2H2BF	0x0
360	chr1	149513523	149514749	−	HIST2H2BF	0x0
361	chr1	149803642	149804974	+	HIST2H4A	0x0
362	chr1	149803642	149804974	+	HIST2H4B	0x0
363	chr1	149822551	149824705	+	HIST2H2AA3	0x0
364	chr1	149822551	149824705	+	HIST2H2AA4	0x0
365	chr1	149822551	149824705	+	HIST2H3A	0x0
366	chr1	149822551	149824705	+	HIST2H3C	0x0
367	chr1	149857574	149858794	−	HIST2H2BE	0x0
368	chr1	149858006	149859450	+	HIST2H2AC	0x0
369	chr1	150190301	150191593	−	ANP32E	0x0
370	chr1	150208744	150210050	+	CA14	0x0
371	chr1	150324926	150326093	+	PRPF3	0x0
372	chr1	150418223	150419437	+	RPRD2	0x0
373	chr1	150445729	150446920	+	RPRD2	0x0
374	chr1	150464353	150465522	+	TARS2	0x0
375	chr1	150470489	150471707	+	TARS2	0x0
376	chr1	150548808	150549982	−	MCL1	0x0
377	chr1	150592648	150593816	−	ENSA	0x0
378	chr1	150594619	150595719	−	ENSA	0x0
379	chr1	150815378	150816598	−	ARNT	0x2
380	chr1	150901999	150903198	+	SETDB1	0x0
381	chr1	150937624	150938971	−	CERS2	0x0
382	chr1	151024631	151025836	−	CDC42SE1	0x0
383	chr1	151148459	151149816	−	TMOD4	0x0
384	chr1	151148459	151149816	−	VPS72	0x0
385	chr1	151214030	151215213	+	PIP5K1A	0x0
386	chr1	151377945	151379168	−	POGZ	0x0
387	chr1	151415600	151416737	−	POGZ	0x0
388	chr1	151424674	151425882	−	POGZ	0x0
389	chr1	151669554	151671784	+	SNX27	0x0
390	chr1	153608927	153610327	+	CHTOP	0x0
391	chr1	153637282	153638518	−	ILF2	0x0
392	chr1	153949216	153950397	−	JTB	0x0
393	chr1	154179204	154180520	−	C1orf43	0x0
394	chr1	154223078	154224555	+	UBAP2L	0x0
395	chr1	154229465	154230671	+	UBAP2L	0x0
396	chr1	154231629	154232898	+	UBAP2L	0x0
397	chr1	154554155	154556592	−	ADAR	0x0
398	chr1	154573661	154574860	−	ADAR	0x0
399	chr1	154744040	154745218	−	KCNN3	0x2
400	chr1	155092389	155093588	+	EFNA1	0x1
401	chr1	155216724	155217968	−	FAM189B	0x0
402	chr1	155222866	155224055	−	FAM189B	0x0
403	chr1	155238484	155239665	−	CLK2	0x0
404	chr1	155281808	155283956	+	FDPS	0x0
405	chr1	155387707	155388905	−	ASH1L	0x0
406	chr1	155392166	155393369	−	ASH1L	0x0
407	chr1	155628831	155630008	−	YY1AP1	0x0
408	chr1	155717315	155718435	−	GON4L	0x0
409	chr1	155734656	155735997	−	GON4L	0x0
410	chr1	155889121	155890387	−	SNORA42	0x0
411	chr1	155895194	155896426	−	KIAA0907	0x0
412	chr1	155895194	155896426	−	SCARNA4	0x0
413	chr1	155978393	155979751	−	SSR2	0x0
414	chr1	156005184	156006501	−	UBQLN4	0x0
415	chr1	156046144	156047385	−	MEX3A	0x0
416	chr1	156049971	156051157	−	MEX3A	0x0
417	chr1	156083983	156085214	+	LMNA	0x0
418	chr1	156711443	156713262	−	HDGF	0x0
419	chr1	159147726	159148925	+	CADM3	0x1
420	chr1	159887640	159888903	−	TAGLN2	0x0
421	chr1	160247969	160249354	−	PEX19	0x0
422	chr1	160323451	160324651	+	NCSTN	0x0
423	chr1	160964965	160966160	−	F11R	0x0
424	chr1	160967011	160968217	−	F11R	0x0
425	chr1	161140861	161142038	−	B4GALT3	0x0
426	chr1	161195560	161196876	+	TOMM40L	0x0
427	chr1	161287359	161288596	+	SDHC	0x2
428	chr1	161296677	161298830	+	SDHC	0x2
429	chr1	161409368	161410591	−	C1orf192	0x0
430	chr1	161500321	161501624	+	HSPA6	0x4
431	chr1	161581923	161583137	+	HSPA7	0x0
432	chr1	161590868	161592139	+	HSPA7	0x0
433	chr1	162470267	162471488	+	UHMK1	0x0
434	chr1	164569061	164570291	+	PBX1	0x2
435	chr1	165825882	165827031	+	UCK2	0x0
436	chr1	165878681	165880175	+	UCK2	0x0
437	chr1	166245062	166246377	−	FAM78B	0x0
438	chr1	166716741	166718458	+	POGK	0x0
439	chr1	166822396	166823563	+	POGK	0x0
440	chr1	167876363	167877573	−	ADCY10	0x0
441	chr1	168024779	168025960	−	GPR161	0x0
442	chr1	168218537	168219697	+	SFT2D2	0x0
443	chr1	169894169	169895391	−	KIFAP3	0x0
444	chr1	171470726	171471915	+	PRRC2C	0x0
445	chr1	171509758	171510953	+	PRRC2C	0x0
446	chr1	173760137	173761357	+	KLHL20	0x0
447	chr1	173832715	173837436	−	GAS5	0x1
448	chr1	173832715	173837436	−	SNORD44	0x0
449	chr1	173832715	173837436	−	SNORD47	0x0
450	chr1	173832715	173837436	−	SNORD74	0x0
451	chr1	173832715	173837436	−	SNORD75	0x0
452	chr1	173832715	173837436	−	SNORD76	0x0
453	chr1	173832715	173837436	−	SNORD77	0x0
454	chr1	173832715	173837436	−	SNORD78	0x0
455	chr1	173832715	173837436	−	SNORD79	0x0
456	chr1	173832715	173837436	−	SNORD80	0x0
457	chr1	173832715	173837436	−	SNORD81	0x0
458	chr1	173903892	173905070	−	RC3H1	0x0
459	chr1	173906989	173908288	−	RC3H1	0x0
460	chr1	174158307	174159546	+	RABGAP1L	0x0
461	chr1	178567950	178569162	+	C1orf220	0x0
462	chr1	178842862	178844097	+	RALGPS2	0x0
463	chr1	178886248	178887421	+	RALGPS2	0x0
464	chr1	179189773	179190983	−	ABL2	0x2
465	chr1	179813512	179814723	−	TOR1AIP2	0x0
466	chr1	179833159	179835492	−	TOR1AIP2	0x0
467	chr1	180080290	180081489	+	CEP350	0x0
468	chr1	180245669	180246855	−	LOC100527964	0x0
469	chr1	180737011	180738229	+	XPR1	0x0
470	chr1	180751452	180752652	+	XPR1	0x0
471	chr1	180944787	180946000	−	STX6	0x0
472	chr1	182352152	182354225	−	GLUL	0x0
473	chr1	182357155	182358347	−	GLUL	0x0
474	chr1	182822589	182823780	+	DHX9	0x0
475	chr1	182843646	182844797	+	DHX9	0x0
476	chr1	183451618	183452866	+	SMG7	0x0
477	chr1	183521166	183522365	+	SMG7	0x0
478	chr1	183599093	183600275	−	ARPC5	0x0
479	chr1	185029958	185031201	+	RNF2	0x0
480	chr1	185266746	185267923	−	IVNS1ABP	0x0
481	chr1	186341227	186342433	+	C1orf27	0x0
482	chr1	190328252	190329522	−	FAM5C	0x0
483	chr1	193054036	193055950	+	TROVE2	0x0
484	chr1	194881379	194882556	−	KCNT2	0x0
485	chr1	196246079	196247256	−	KCNT2	0x0
486	chr1	196454168	196455378	−	KCNT2	0x0
487	chr1	197123904	197125081	−	ZBTB41	0x2
488	chr1	198189561	198190790	+	NEK7	0x0
489	chr1	201104044	201105241	−	TMEM9	0x0
490	chr1	201263563	201264762	+	PKP1	0x0
491	chr1	201844844	201846017	+	IPO9	0x0
492	chr1	201846540	201847715	+	IPO9	0x0
493	chr1	202102898	202104120	−	ARL8A	0x0
494	chr1	202112029	202113216	−	ARL8A	0x0
495	chr1	202428654	202429874	+	PPP1R12B	0x0
496	chr1	203292770	203293990	+	BTG2	0x1
497	chr1	203765008	203766264	+	ZC3H11A	0x0
498	chr1	204061645	204062843	+	SOX13	0x0
499	chr1	204082926	204084098	+	SOX13	0x0
500	chr1	204475098	204476336	+	MDM4	0x2
501	chr1	204475595	204476748	−	PIK3C2B	0x0
502	chr1	204506187	204507372	+	MDM4	0x2
503	chr1	204522274	204523452	+	MDM4	0x2
504	chr1	204530962	204532206	−	LRRN2	0x0
505	chr1	205217339	205218722	+	TMCC2	0x0
506	chr1	205273122	205274318	−	NUAK2	0x0
507	chr1	205592298	205593497	−	ELK4	0x2
508	chr1	205682685	205686265	−	NUCKS1	0x0
509	chr1	205686535	205687953	−	NUCKS1	0x0
510	chr1	205718529	205719853	−	NUCKS1	0x0
511	chr1	206518541	206519779	+	SRGAP2	0x0
512	chr1	206895521	206896732	+	MAPKAPK2	0x0
513	chr1	206905648	206907237	+	MAPKAPK2	0x0
514	chr1	207285121	207286300	+	C4BPA	0x0
515	chr1	210029291	210030488	+	DIEXF	0x0
516	chr1	211712199	211713383	−	SLC30A1	0x0
517	chr1	212265961	212267203	+	DTL	0x0
518	chr1	212273532	212274725	+	DTL	0x0
519	chr1	212792678	212793986	+	ATF3	0x0
520	chr1	212964633	212965882	+	TATDN3	0x0
521	chr1	214371742	214372972	+	SMYD2	0x0
522	chr1	214529737	214530959	−	PTPN14	0x4
523	chr1	215758835	215760082	+	KCTD3	0x0
524	chr1	216707533	216708744	−	ESRRG	0x0
525	chr1	216938284	216939482	+	SPATA17	0x0
526	chr1	217781474	217782701	−	GPATCH2	0x0
527	chr1	219464873	219466060	+	LYPIAL1	0x0
528	chr1	220290576	220291740	+	RNU5F-1	0x0
529	chr1	220343726	220344909	−	RAB3GAP2	0x0
530	chr1	220373343	220374520	−	MIR664	0x0
531	chr1	220373343	220374520	−	SNORA36B	0x0
532	chr1	220411787	220412985	−	RAB3GAP2	0x0
533	chr1	224186371	224187597	+	FBXO28	0x0
534	chr1	224458091	224459318	−	NVL	0x0
535	chr1	224487715	224488892	−	NVL	0x0
536	chr1	224621339	224622694	−	WDR26	0x0
537	chr1	224632047	224633294	+	CNIH4	0x0
538	chr1	225227059	225228271	+	DNAH14	0x0
539	chr1	225395058	225396267	+	DNAH14	0x0
540	chr1	225589675	225591446	−	LBR	0x0
541	chr1	225683421	225684835	−	ENAH	0x0
542	chr1	225699878	225701146	−	ENAH	0x0
543	chr1	225832972	225834130	−	ENAH	0x0
544	chr1	225839667	225840854	−	ENAH	0x0
545	chr1	225840886	225842085	−	ENAH	0x0
546	chr1	225976535	225978191	+	SRP9	0x0
547	chr1	226053350	226054557	−	TMEM63A	0x0
548	chr1	226231274	226232493	+	H3F3A	0x0
549	chr1	226308957	226310189	+	H3F3A	0x0
550	chr1	226308957	226310189	+	H3F3AP4	0x0
551	chr1	226332364	226333539	−	ACBD3	0x0
552	chr1	226548198	226550310	−	PARP1	0x0
553	chr1	226633087	226634318	+	C1orf95	0x0
554	chr1	226764909	226766092	+	C1orf95	0x0
555	chr1	227174238	227175480	+	ADCK3	0x0
556	chr1	228246176	228247405	+	WNT3A	0x0
557	chr1	228268372	228269597	−	C1orf35	0x0
558	chr1	228286031	228287395	+	ARF1	0x1
559	chr1	228460035	228461227	+	OBSCN	0x6
560	chr1	228464213	228465383	+	OBSCN	0x6
561	chr1	228479225	228480392	+	OBSCN	0x6
562	chr1	228588834	228589997	−	TRIM11	0x0
563	chr1	228742937	228744191	+	RHOU	0x0
564	chr1	228763318	228764571	−	HIST3H2A	0x0
565	chr1	228822584	228823835	+	DUSP5P	0x0
566	chr1	229452464	229453715	+	SPHAR	0x0
567	chr1	229829043	229830261	+	URB2	0x0
568	chr1	230376361	230377564	+	GALNT2	0x0
569	chr1	231076229	231077435	−	TTC13	0x0
570	chr1	231089569	231090749	−	TTC13	0x0
571	chr1	231113282	231114478	−	TTC13	0x0
572	chr1	231400510	231401943	+	GNPAT	0x0
573	chr1	231694808	231696046	+	TSNAX	0x0
574	chr1	231694808	231696046	+	TSNAX-DISC1	0x0
575	chr1	231990122	231991288	+	DISC1	0x0
576	chr1	233514316	233515555	+	KIAA1804	0x2
577	chr1	233518262	233519476	+	KIAA1804	0x2
578	chr1	233520067	233521316	+	KIAA1804	0x2
579	chr1	234492209	234493429	−	TARBP1	0x0
580	chr1	234496426	234497849	+	C1orf31	0x0
581	chr1	234563407	234565919	−	TARBP1	0x0
582	chr1	234585710	234586893	−	TARBP1	0x0
583	chr1	234605372	234606597	−	TARBP1	0x0
584	chr1	234610314	234611484	−	TARBP1	0x0
585	chr1	234613342	234614518	−	TARBP1	0x0
586	chr1	234741314	234743389	−	IRF2BP2	0x0
587	chr1	234745312	234746411	−	IRF2BP2	0x0
588	chr1	235272366	235273548	−	TOMM20	0x0
589	chr1	235273910	235275525	−	TOMM20	0x0
590	chr1	235290593	235291716	−	SNORA14B	0x0
591	chr1	235460844	235462024	−	ARID4B	0x0
592	chr1	235601456	235602682	+	TBCE	0x0
593	chr1	235796415	235797938	−	GNG4	0x0
594	chr1	236380467	236381595	−	ERO1LB	0x0
595	chr1	236430556	236431809	+	GPR137B	0x0
596	chr1	236646542	236647719	+	EDARADD	0x0
597	chr1	236706956	236708213	−	HEATR1	0x0
598	chr1	236961224	236962464	+	MTR	0x0
599	chr1	236975460	236976657	+	MTR	0x0
600	chr1	237007214	237008501	+	MTR	0x0
601	chr1	237765743	237767229	+	RYR2	0x2
602	chr1	243663467	243665403	−	AKT3	0x2
603	chr1	244586559	244587735	−	ADSS	0x0
604	chr1	244871059	244872312	+	PPPDE1	0x0
605	chr1	245013374	245014444	−	HNRNPU	0x2
606	chr1	245016406	245017772	−	HNRNPU	0x2
607	chr1	245020748	245021936	−	HNRNPU	0x2
608	chr1	245026904	245028090	−	HNRNPU	0x2
609	chr1	245106873	245108219	+	EFCAB2	0x0
610	chr1	245382092	245383296	+	KIF26B	0x0
611	chr1	246197368	246198550	−	SMYD3	0x0
612	chr1	246349541	246350748	−	SMYD3	0x0
613	chr1	246636841	246638018	−	SMYD3	0x0
614	chr1	247318878	247320068	−	ZNF124	0x0
615	chr1	247322465	247323700	−	ZNF124	0x0
616	chr1	247326069	247327168	−	ZNF124	0x0
617	chr1	247453655	247454860	−	ZNF496	0x0
618	chr1	247613596	247614816	+	NLRP3	0x2
619	chr1	249167501	249168976	+	ZNF672	0x0
620	chr10	327413	328640	−	DIP2C	0x0
621	chr10	666729	667894	−	DIP2C	0x0
622	chr10	717319	718546	−	DIP2C	0x0
623	chr10	851188	852361	−	LARP4B	0x0
624	chr10	857811	858983	−	LARP4B	0x0
625	chr10	897946	899153	−	LARP4B	0x0
626	chr10	915522	916733	−	LARP4B	0x0
627	chr10	1037878	1039077	+	GTPBP4	0x1
628	chr10	1177466	1178635	+	WDR37	0x0
629	chr10	3143076	3144273	+	PFKP	0x2
630	chr10	5498718	5499855	+	NET1	0x0
631	chr10	5894873	5896267	−	ANKRD16	0x0
632	chr10	7284973	7286228	−	SFMBT2	0x4
633	chr10	7318329	7319540	−	SFMBT2	0x4
634	chr10	7327265	7328458	−	SFMBT2	0x4
635	chr10	7361094	7362349	−	SFMBT2	0x4
636	chr10	7388629	7389823	−	SFMBT2	0x4
637	chr10	7884436	7885634	+	TAF3	0x0
638	chr10	8034661	8035813	+	TAF3	0x0
639	chr10	10817881	10819050	−	SFTA1P	0x0
640	chr10	11375072	11376197	+	CELF2	0x0
641	chr10	11529210	11530389	−	USP6NL	0x0
642	chr10	12139258	12140488	+	DHTKD1	0x0
643	chr10	12141598	12142790	+	DHTKD1	0x0
644	chr10	12193739	12194931	+	SEC61A2	0x0
645	chr10	13769281	13770472	+	PRPF18	0x0
646	chr10	15254670	15255759	−	FAM171A1	0x0
647	chr10	15677400	15678528	−	ITGA8	0x0
648	chr10	15885198	15886387	−	FAM188A	0x1
649	chr10	16512344	16513511	+	PTER	0x0
650	chr10	16517452	16518631	+	PTER	0x0
651	chr10	17271274	17272447	+	VIM	0x0
652	chr10	17278801	17280000	+	VIM	0x0
653	chr10	17658065	17659244	−	PTPLA	0x0
654	chr10	17693625	17694846	+	StAM	0x0
655	chr10	18731218	18732413	+	CACNB2	0x0
656	chr10	18969440	18970539	+	ARL5B	0x0
657	chr10	21442123	21443301	−	C10orf113	0x0
658	chr10	21453958	21455156	+	LOC100128511	0x0
659	chr10	21934560	21935750	+	MLLT10	0x0
660	chr10	21944578	21945780	+	MLLT10	0x0
661	chr10	21974309	21975409	+	MLLT10	0x0
662	chr10	22221492	22222711	+	MLLT10	0x0
663	chr10	22517892	22519075	−	EBLN1	0x0
664	chr10	27046890	27048090	+	PDSS1	0x0
665	chr10	27112344	27113521	−	ABI1	0x2
666	chr10	27414860	27416037	−	YME1L1	0x0
667	chr10	27422424	27423599	−	YME1L1	0x0
668	chr10	27430769	27431910	−	YME1L1	0x0
669	chr10	27484861	27486047	−	ACBD5	0x0
670	chr10	27529727	27530930	−	ACBD5	0x0
671	chr10	27828011	27829181	+	RAB18	0x0
672	chr10	28840201	28841312	+	WAC	0x0
673	chr10	28896605	28897768	+	WAC	0x0
674	chr10	30601620	30602784	−	MTPAP	0x0
675	chr10	32197132	32198312	−	ARHGAP12	0x0
676	chr10	32298882	32300844	−	KIF5B	0x2
677	chr10	32307631	32308819	−	KIF5B	0x2
678	chr10	32599864	32601121	−	EPC1	0x2
679	chr10	33532312	33533462	−	NRP1	0x0
680	chr10	34682668	34684029	−	PARD3	0x0
681	chr10	34931805	34940500	−	PARD3	0x0
682	chr10	35005954	35007146	−	PARD3	0x0
683	chr10	35674327	35675517	+	CCNY	0x0
684	chr10	38104286	38105423	−	ZNF248	0x0
685	chr10	38410549	38411702	+	ZNF37A	0x2
686	chr10	38726021	38727193	+	LOC399744	0x0
687	chr10	42987909	42989114	+	LOC848S6	0x0
688	chr10	43047320	43048711	−	ZNF37BP	0x0
689	chr10	45950107	45951270	−	MARCH8	0x0
690	chr10	48205645	48206744	+	AGAP9	0x0
691	chr10	49862031	49863217	−	ARHGAP22	0x0
692	chr10	50910581	50911972	−	OGDHL	0x0
693	chr10	51387116	51388251	+	MSMB	0x1
694	chr10	51591654	51592946	−	TIMM23	0x0
695	chr10	51748030	51749191	+	AGAP6	0x0
696	chr10	52141798	52142974	−	SGMS1	0x0
697	chr10	52789097	52790200	+	PRKG1	0x0
698	chr10	52938396	52939541	+	PRKG1	0x0
699	chr10	52980093	52981305	+	PRKG1	0x0
700	chr10	52999596	53000733	+	MIR605	0x0
701	chr10	53089007	53090231	+	MIR605	0x0
702	chr10	53134151	53135349	+	MIR605	0x0
703	chr10	53342480	53343660	+	PRKG1	0x0
704	chr10	53412101	53413200	+	PRKG1	0x0
70S	chr10	53426903	53428121	+	PRKG1	0x0
706	chr10	57419102	57420322	−	ZWINT	0x0
707	chr10	57526788	57528007	−	ZWINT	0x0
708	chr10	58117180	58118473	−	ZWINT	0x0
709	chr10	61550012	61551187	−	CCDC6	0x0
710	chr10	61646660	61647838	−	CCDC6	0x0
711	chr10	61799473	61800681	−	ANK3	0x2
712	chr10	62471757	62472934	−	ANK3	0x2
713	chr10	62553173	62554457	−	CDK1	0x0
714	chr10	62670575	62671753	−	RHOBTB1	0x0
715	chr10	63447839	63449050	+	C10orf107	0x0
716	chr10	63976408	63977620	−	RTKN2	0x0
717	chr10	65006684	65007886	−	JMJD1C	0x0
718	chr10	65256338	65257454	−	JMJD1C	0x0
719	chr10	65283600	65284816	+	REEP3	0x0
720	chr10	65358845	65360025	+	REEP3	0x0
721	chr10	65381754	65383090	+	REEP3	0x0
722	chr10	67420760	67421880	−	CTNNA3	0x4
723	chr10	69090896	69092095	−	CTNNA3	0x4
724	chr10	69523738	69525755	+	SIRT1	0x0
725	chr10	69556175	69557381	−	DNAJC12	0x0
726	chr10	70101826	70103014	+	HNRNPH3	0x0
727	chr10	70128501	70129686	−	RUFY2	0x0
728	chr10	70153037	70154136	−	RUFY2	0x0
729	chr10	70227468	70228610	−	DNA2	0x0
730	chr10	70286378	70287515	−	SLC25A16	0x0
731	chr10	70416334	70417482	+	TET1	0x0
732	chr10	70425287	70426442	+	TET1	0x0
733	chr10	70458278	70459445	+	TET1	0x0
734	chr10	70514348	70515593	+	CCAR1	0x0
735	chr10	70514348	70515593	+	SNORD98	0x0
736	chr10	70521337	70522505	+	CCAR1	0x0
737	chr10	70526118	70527353	+	CCAR1	0x0
738	chr10	70547382	70548611	+	CCAR1	0x0
739	chr10	70719311	70720548	+	DDX21	0x0
740	chr10	70742633	70743716	+	DDX21	0x0
741	chr10	71213672	71214905	+	TSPAN15	0x0
742	chr10	71968827	71969932	−	PPA1	0x0
743	chr10	72090161	72091301	−	LRRC20	0x0
744	chr10	72179181	72180412	+	EIF4EBP2	0x0
745	chr10	72182095	72183256	+	EIF4EBP2	0x0
746	chr10	72186344	72188291	+	EIF4EBP2	0x0
747	chr10	72226248	72227487	+	KIAA1274	0x0
748	chr10	72327126	72328451	+	KIAA1274	0x0
749	chr10	72603792	72604923	+	SGPL1	0x0
750	chr10	72638485	72639719	+	SGPL1	0x0
751	chr10	73059524	73060994	+	UNC5B	0x1
752	chr10	73575664	73577723	−	PSAP	0x0
753	chr10	73769977	73771076	+	CHST3	0x0
754	chr10	73771572	73773721	+	CHST3	0x0
755	chr10	74226979	74228171	−	MICU1	0x0
756	chr10	74645466	74646663	+	MCU	0x0
757	chr10	74761035	74762200	−	P4HA1	0x0
758	chr10	74853987	74855251	−	P4HA1	0x0
759	chr10	75008449	75009792	−	MRPS16	0x0
760	chr10	75262821	75263997	−	USP54	0x0
761	chr10	75433909	75435129	−	AGAP5	0x0
762	chr10	75456729	75457933	−	AGAP5	0x0
763	chr10	75536646	75537837	+	FUT11	0x0
764	chr10	75545273	75546461	+	KIAA0913	0x0
765	chr10	75558239	75559455	+	KIAA0913	0x0
766	chr10	75623611	75624834	−	CAMK2G	0x0
767	chr10	75828203	75829447	+	VCL	0x1
768	chr10	76102005	76103155	+	ADK	0x0
769	chr10	76602446	76603781	+	KAT6B	0x2
770	chr10	76870831	76872021	+	SAMD8	0x0
771	chr10	76936412	76937545	+	SAMD8	0x0
772	chr10	76983205	76984301	+	VDAC2	0x0
773	chr10	76994299	76995499	−	COMTD1	0x0
774	chr10	76995165	76996322	+	VDAC2	0x0
775	chr10	77160413	77161591	−	ZNF503	0x0
776	chr10	77550216	77551415	+	C10orf11	0x0
777	chr10	79514310	79515493	−	DLG5	0x2
778	chr10	79550701	79552113	−	DLG5	0x2
779	chr10	79580656	79581853	−	DLG5	0x2
780	chr10	79729156	79730355	−	POLR3A	0x2
781	chr10	79794606	79795831	+	RPS24	0x0
782	chr10	79796462	79797625	+	RPS24	0x0
783	chr10	79799824	79800997	+	RPS24	0x0
784	chr10	80146596	80147772	−	POLR3A	0x2
785	chr10	81572099	81573257	−	SFTPD	0x0
786	chr10	81686310	81687409	+	MBL1P	0x0
787	chr10	81885271	81886500	+	PLAC9	0x0
788	chr10	85911939	85913402	+	GHITM	0x0
789	chr10	87571839	87573088	−	GRID1	0x2
790	chr10	87811722	87812914	+	LOC100507470	0x0
791	chr10	88126165	88127381	+	OPN4	0x0
792	chr10	88256073	88257291	−	WAPAL	0x0
793	chr10	88266884	88268077	−	WAPAL	0x0
794	chr10	88648778	88650011	+	BMPR1A	0x2
795	chr10	89312084	89313511	+	MINPP1	0x0
796	chr10	89512707	89513915	−	ATAD1	0x0
797	chr10	89542693	89544610	−	ATAD1	0x0
798	chr10	89727592	89728794	+	PTEN	0x1
799	chr10	90999167	91000389	+	LIPA	0x0
800	chr10	91144482	91145707	−	SLC16A12	0x0
801	chr10	92986428	92987533	+	PCGF5	0x0
802	chr10	93576218	93577444	+	TNKS2	0x0
803	chr10	93756841	93758040	+	BTAF1	0x0
804	chr10	94044068	94045250	−	CPEB3	0x0
805	chr10	94092672	94093873	+	MARCH5	0x0
806	chr10	94193802	94195017	−	MARK2P9	0x0
807	chr10	94685206	94686408	+	EXOC6	0x0
808	chr10	96108489	96109640	−	NOC3L	0x0
809	chr10	96117423	96118595	−	NOC3L	0x0
810	chr10	96122067	96123244	−	NOC3L	0x0
811	chr10	96349622	96350815	+	HELLS	0x0
812	chr10	96362603	96364743	+	HELLS	0x0
813	chr10	96370239	96371467	+	HELLS	0x0
814	chr10	97888941	97890188	+	ZNF518A	0x2
815	chr10	98038160	98039356	+	DNTT	0x0
816	chr10	98281270	98282442	−	TM9SF3	0x0
817	chr10	98352618	98353841	−	PIK3AP1	0x0
818	chr10	98560827	98562069	−	PIK3AP1	0x0
819	chr10	98619000	98620163	+	LCOR	0x0
820	chr10	98697481	98698689	+	LCOR	0x0
821	chr10	99200150	99201299	−	EXOSC1	0x0
822	chr10	99211300	99212538	+	ZDHHC16	0x0
823	chr10	99220768	99221879	−	MMS19	0x0
824	chr10	99257035	99258187	−	MMS19	0x0
825	chr10	99434051	99435229	−	AVPI1	0x2
826	chr10	99486666	99487852	+	MARVELD1	0x0
827	chr10	99620012	99621179	+	GOLGA7B	0x0
828	chr10	101106408	101107648	+	CNNM1	0x0
829	chr10	101189707	101190895	−	GOT1	0x0
830	chr10	101198213	101199432	+	CNNM1	0x0
831	chr10	101446019	101447252	+	ENTPD7	0x0
832	chr10	101909566	101910739	−	ERLIN1	0x0
833	chr10	101996380	101997710	−	CWF19L1	0x0
834	chr10	101996380	101997710	−	SNORA12	0x0
835	chr10	102012574	102013761	−	CWF19L1	0x0
836	chr10	102121124	102123864	+	SCD	0x0
837	chr10	102123929	102124967	+	SCD	0x0
838	chr10	102312573	102313722	+	HIF1AN	0x0
839	chr10	102510249	102511465	+	PAX2	0x0
840	chr10	102588417	102589613	+	PAX2	0x0
841	chr10	102740219	102741347	−	MRPL43	0x0
842	chr10	102746626	102747726	−	MRPL43	0x0
843	chr10	102826216	102827396	+	KAZALD1	0x0
844	chr10	103066793	103067972	−	BTRC	0x0
845	chr10	103124035	103125312	−	LBX1	0x0
846	chr10	103432736	103433950	−	FBXW4	0x0
847	chr10	103732741	103733962	−	C10orf76	0x0
848	chr10	103870177	103871418	−	LDB1	0x6
849	chr10	103903555	103904683	+	PPRC1	0x0
850	chr10	104350740	104351950	+	SUFU	0x1
851	chr10	104391364	104392863	+	SUFU	0x1
852	chr10	104618319	104619522	+	C10orf32	0x0
853	chr10	104618319	104619522	+	C10orf32-AS3MT	0x0
854	chr10	104703041	104704186	+	CNNM2	0x0
855	chr10	104841572	104842768	+	CNNM2	0x0
856	chr10	104929881	104931142	−	NT5C2	0x0
857	chr10	104936094	104937308	+	LOC729020	0x0
858	chr10	104966476	104967641	−	NT5C2	0x0
859	chr10	105071657	105072830	−	PCGF6	0x0
860	chr10	105236366	105237543	−	CALHM3	0x0
861	chr10	105354565	105355675	−	SH3PXD2A	0x0
862	chr10	105359058	105360157	−	SH3PXO2A	0x0
863	chr10	105402766	105403933	−	SH3PXD2A	0x0
864	chr10	105753471	105754685	+	SLK	0x0
865	chr10	105797373	105798600	+	SLK	0x0
866	chr10	108729213	108730449	+	SORCS3	0x0
867	chr10	111825059	111826221	+	ADD3	0x0
868	chr10	112045697	112046917	+	MXI1	0x1
869	chr10	112541004	112542127	+	RBM20	0x0
870	chr10	112556693	112557891	+	RBM20	0x0
871	chr10	112601898	112603122	−	LOC282997	0x0
872	chr10	114300308	114301485	+	VTI1A	0x2
873	chr10	114430666	114431996	+	VTI1A	0x2
874	chr10	114575897	114577131	+	VTI1A	0x2
875	chr10	114803679	114804834	+	TCF7L2	0x1
876	chr10	114810783	114812085	+	TCF7L2	0x1
877	chr10	114832960	114834173	+	TCF7L2	0x1
878	chr10	114994467	114995686	+	TCF7L2	0x1
879	chr10	116191291	116192572	−	ABLIM1	0x0
880	chr10	116192892	116194131	−	ABLIM1	0x0
881	chr10	116194170	116195533	−	ABLIM1	0x0
882	chr10	116482750	116483970	+	FAM160B1	0x0
883	chr10	116726306	116727502	+	TRUB1	0x0
884	chr10	118432853	118434126	−	HSPA12A	0x0
885	chr10	118659202	118660345	−	KIAA1598	0x0
886	chr10	118672336	118673543	−	KIAA1598	0x0
887	chr10	119040865	119042286	−	PDZD8	0x0
888	chr10	119133806	119134993	−	PDZD8	0x0
889	chr10	119613911	119615133	−	RAB11FIP2	0x0
890	chr10	120444662	120445977	−	C10orf46	0x0
891	chr10	120801317	120802788	−	EIF3A	0x2
892	chr10	120827133	120828353	+	NANOS1	0x0
893	chr10	120829962	120831338	−	EIF3A	0x2
894	chr10	120928180	120929329	−	PRDX3	0x0
895	chr10	121334411	121335594	−	TIAL1	0x0
896	chr10	121335956	121337136	−	TIAL1	0x0
897	chr10	121608403	121609588	−	MCMBP	0x0
898	chr10	123310751	123311964	−	FGFR2	0x2
899	chr10	123324439	123325692	−	FGFR2	0x2
900	chr10	123663896	123665105	−	ATE1	0x0
901	chr10	123718953	123720157	−	NSMCE4A	0x0
902	chr10	124913829	124915052	+	BUB3	0x0
903	chr10	124924070	124925428	+	BUB3	0x0
904	chr10	124934702	124936353	+	BUB3	0x0
905	chr10	124991437	124992665	+	BUB3	0x0
906	chr10	125025863	125027036	+	BUB3	0x0
907	chr10	125114673	125115921	+	BUB3	0x0
908	chr10	125164937	125166171	+	BUB3	0x0
909	chr10	125198504	125199751	+	GPR26	0x0
910	chr10	125664056	125665258	−	CPXM2	0x0
911	chr10	125774837	125776019	−	CHST15	0x0
912	chr10	125830388	125831664	−	CHST15	0x0
913	chr10	126308995	126312062	−	FAM53B	0x0
914	chr10	126369856	126371487	−	FAM53B	0x0
915	chr10	126464474	126465618	−	METTL10	0x0
916	chr10	126475775	126476905	−	METTL10	0x0
917	chr10	126496071	126497298	+	FAM175B	0x0
918	chr10	126700536	126701714	−	CTBP2	0x1
919	chr10	126800984	126802132	−	CTBP2	0x1
920	chr10	126816411	126817597	−	CTBP2	0x1
921	chr10	127411064	127412263	+	C10orf137	0x2
922	chr10	127705459	127706666	−	ADAM12	0x2
923	chr10	128854346	128855588	+	DOCK1	0x0
924	chr10	129894800	129896956	−	MKI67	0x0
925	chr10	129905232	129906521	−	MKI67	0x0
926	chr10	129913111	129914504	−	MKI67	0x0
927	chr10	131634425	131635894	−	EBF3	0x0
928	chr10	131642924	131644143	+	MGMT	0x0
929	chr10	132107642	132108887	+	GLRX3	0x0
930	chr10	132179372	132180570	−	LOC387723	0x0
931	chr10	134109868	134111045	−	STK32C	0x0
932	chr10	134754867	134756042	−	TTC40	0x0
933	chr10	135095771	135096937	−	TUBGCP2	0x0
934	chr10	135115703	135116996	−	TUBGCP2	0x0
935	chr10	135121757	135122955	−	TUBGCP2	0x0
936	chr10	135222774	135224017	+	MTG1	0x0
937	chr11	290224	291416	+	ATHL1	0x0
938	chr11	439910	441128	−	ANO9	0x0
939	chr11	642177	643361	−	DEAF1	0x0
940	chr11	671065	672334	−	DEAF1	0x0
941	chr11	769924	771342	−	PDDC1	0x0
942	chr11	790565	791735	−	SLC25A22	0x0
943	chr11	809719	810944	+	RPLP2	0x0
944	chr11	811175	813388	+	RPLP2	0x0
945	chr11	811175	813388	+	SNORA52	0x0
946	chr11	988708	989919	+	AP2A2	0x0
947	chr11	1773934	1775128	−	CTSD	0x0
948	chr11	2393292	2394489	+	CD81	0x4
949	chr11	2417707	2419006	+	CD81	0x4
950	chr11	2984521	2985619	−	SNORA54	0x0
951	chr11	3383623	3384799	−	ZNF195	0x0
952	chr11	3716135	3717338	−	NUP98	0x2
953	chr11	6631438	6632537	−	TAF10	0x0
954	chr11	8125426	8126565	+	TUB	0x0
955	chr11	8538631	8539771	−	STK33	0x0
956	chr11	8689247	8690420	−	TRIM66	0x0
957	chr11	8705244	8706446	+	RPL27A	0x0
958	chr11	8705244	8706446	+	SNORA3	0x0
959	chr11	8706452	8707671	+	RPL27A	0x0
960	chr11	8706452	8707671	+	SNORA45	0x0
961	chr11	9310545	9311720	−	TMEM41B	0x0
962	chr11	9431002	9432103	+	IPO7	0x0
963	chr11	9449754	9451088	+	IPO7	0x0
964	chr11	9449754	9451088	+	SNORA23	0x0
965	chr11	9461513	9462627	+	IPO7	0x0
966	chr11	9609488	9610703	+	WEE1	0x0
967	chr11	10264434	10265657	−	SBF2	0x0
968	chr11	10529526	10530696	−	MIR4485	0x0
969	chr11	10529526	10530696	−	MTRNR2L8	0x0
970	chr11	10818436	10819796	−	EIF4G2	0x0
971	chr11	10822497	10823700	−	EIF4G2	0x0
972	chr11	10822497	10823700	−	SNORD97	0x0
973	chr11	12962124	12963416	+	TEAD1	0x0
974	chr11	13434590	13435724	−	BTBD10	0x0
975	chr11	13440526	13441707	−	BTBd10	0x0
976	chr11	14478587	14479807	−	COPB1	0x0
977	chr11	16760098	16761286	+	C11or158	0x0
978	chr11	16995727	16997058	−	PLEKHA7	0x0
979	chr11	17095623	17098089	−	RPS13	0x0
980	chr11	17098092	17099231	−	RPS13	0x0
981	chr11	17225281	17226466	−	PIK3C2A	0x0
982	chr11	17399390	17400490	+	B7H6	0x0
983	chr11	18428322	18429599	+	LDHA	0x0
984	chr11	19422875	19424100	−	NAV2-AS4	0x0
985	chr11	22248369	22249579	+	ANO5	0x0
986	chr11	22709343	22710553	+	GAS2	0x0
987	chr11	22795836	22797053	+	GAS2	0x0
988	chr11	23427115	23428335	+	GAS2	0x0
989	chr11	28191782	28193016	+	METTL15	0x0
990	chr11	28592373	28593592	+	METTL15	0x0
991	chr11	32608006	32609259	+	EIF3M	0x0
992	chr11	33100090	33101473	+	LINC00294	0x0
993	chr11	33160995	33162510	−	CSTF3	0x0
994	chr11	33690488	33691795	+	C11orf41	0x0
995	chr11	34073293	34074505	+	CAPRIN1	0x0
996	chr11	34117590	34118706	+	CAPRIN1	0x0
997	chr11	34121064	34122602	+	CAPRIN1	0x0
998	chr11	34368183	34369357	−	ABTB2	0x0
999	chr11	35473459	35474657	−	PAMR1	0x0
1000	chr11	36248223	36249497	+	LDLRAD3	0x0
1001	chr11	38594065	38595243	+	C11orf74	0x0
1002	chr11	43465120	43466265	+	TTC17	0x0
1003	chr11	43701813	43703100	+	HSD17B12	0x0
1004	chr11	43710889	43712096	+	HSD17B12	0x0
1005	chr11	43713719	43714879	+	HSD17B12	0x0
1006	chr11	44104241	44105440	+	ACCS	0x0
1007	chr11	44147814	44149025	+	EXT2	0x1
1008	chr11	44950191	44951341	+	TSPAN18	0x0
1009	chr11	44953860	44955070	−	TP53I11	0x0
1010	chr11	45923521	45924726	+	MAPK8IP1	0x0
1011	chr11	46449763	46450915	−	AMBRA1	0x0
1012	chr11	46514646	46515836	−	AMBRA1	0x0
1013	chr11	46699392	46700538	−	ARHGAP1	0x0
1014	chr11	46772535	46773582	−	CKAP5	0x0
1015	chr11	47489352	47490908	−	CELF1	0x0
1016	chr11	47499886	47501080	−	CELF1	0x0
1017	chr11	47509722	47511032	−	CELF1	0x0
1018	chr11	47600235	47601463	+	NDUFS3	0x0
1019	chr11	47799968	47801080	−	NUP160	0x0
1020	chr11	47833349	47834567	−	NUP160	0x0
1021	chr11	50048802	50050001	+	OR4C13	0x2
1022	chr11	57083573	57084694	−	TNKS1BP1	0x0
1023	chr11	57092908	57094413	−	SSRP1	0x0
1024	chr11	57101422	57102590	−	SSRP1	0x0
1025	chr11	57507709	57508876	+	C11orf31	0x0
1026	chr11	57507709	57508876	+	TMX2	0x0
1027	chr11	57538522	57539710	+	CTNND1	0x1
1028	chr11	57575280	57576487	+	CTNND1	0x1
1029	chr11	57575280	57575487	+	TMX2-CTNND1	0x0
1030	chr11	57585111	57586193	+	CTNND1	0x1
1031	chr11	57585111	57586193	+	TMX2-CTNND1	0x0
1032	chr11	58385311	58385651	+	ZFP91	0x0
1033	chr11	59382267	59383461	−	OSBP	0x0
1034	chr11	60657745	60658974	−	PRPF19	0x0
1035	chr11	60673362	60574576	−	PRPF19	0x0
1036	chr11	60905662	60907001	−	VPS37C	0x0
1037	chr11	61080978	61082137	−	DDB1	0x0
1038	chr11	61094557	61095688	−	DDB1	0x0
1039	chr11	61103262	61104457	+	DAK	0x0
1040	chr11	61116305	61117482	−	CYBASC3	0x0
1041	chr11	61171066	61172241	−	CPSF7	0x0
1042	chr11	61570746	61572017	−	FADS1	0x0
1043	chr11	61633292	61634749	+	FADS2	0x0
1044	chr11	61731955	61733169	−	FTH1	0x0
1045	chr11	61918917	61920151	+	INCENP	0x0
1046	chr11	62326613	62327797	−	EEF1G	0x0
1047	chr11	62326613	62327797	−	MIR3654	0x0
1048	chr11	62328614	62329742	−	EEF1G	0x0
1049	chr11	62334335	62335539	−	EEF1G	0x0
1050	chr11	62360207	62361316	−	MTA2	0x2
1051	chr11	62364348	62365556	−	MTA2	0x2
1052	chr11	62383240	62384372	−	B3GAT3	0x0
1053	chr11	62400036	62401262	−	GANAB	0x0
1054	chr11	62431867	62433201	−	C11orf48	0x0
1055	chr11	62432354	62433550	−	METTL12	0x0
1056	chr11	62432354	62433550	+	SNORA57	0x0
1057	chr11	62489249	62490426	+	HNRNPUL2	0x0
1058	chr11	62489249	62490426	−	HNRNPUL2-BSCL2	0x0
1059	chr11	62510820	62512038	+	TTC9C	0x0
1060	chr11	62532031	62533274	+	POLR2G	0x0
1061	chr11	62542758	62543857	+	TAF6L	0x0
1062	chr11	62549124	62550223	+	TAF6L	0x0
1063	chr11	62567012	62568190	−	NXF1	0x2
1064	chr11	62608541	62609849	−	WDR74	0x0
1065	chr11	62618968	62621378	−	SNHG1	0x0
1066	chr11	62618968	62621378	−	SNORD22	0x0
1067	chr11	62618968	62621378	−	SNORD29	0x0
1068	chr11	62618968	62621378	−	SNORD30	0x0
1069	chr11	62618968	62621378	−	SNORD31	0x0
1070	chr11	62622051	62623625	−	SNHG1	0x0
1071	chr11	62622051	62623625	−	SNORD25	0x0
1072	chr11	62622051	62623625	−	SNORD26	0x0
1073	chr11	62622051	62623625	−	SNORD27	0x0
1074	chr11	62622051	62623625	−	SNORD28	0x0
1075	chr11	63423115	63424290	−	ATL3	0x0
1076	chr11	63596428	63597649	+	C11orf84	0x0
1077	chr11	63785551	63786757	−	MACROD1	0x0
1078	chr11	64005477	64006741	+	VEGFB	0x0
1079	chr11	64013805	64014998	−	PPP1R14B	0x0
1080	chr11	64018832	64019978	+	PLCB3	0x1
1081	chr11	64063003	64064157	+	KCNK4	0x0
1082	chr11	64083247	64084373	+	ESRRA	0x0
1083	chr11	64083656	64084870	−	TRMT112	0x0
1084	chr11	64532206	64533405	−	SF1	0x0
1085	chr11	64574182	64575360	−	MEN1	0x1
1086	chr11	64845803	64846957	−	CDCA5	0x0
1087	chr11	64878887	64880037	+	C11orf2	0x0
1088	chr11	64878887	64880037	+	TM7SF2	0x0
1089	chr11	64880221	64881320	+	TM7SF2	0x0
1090	chr11	64914487	64915767	+	MRPL49	0x0
1091	chr11	64978362	64979722	+	CAPN1	0x0
1092	chr11	65197873	65199078	+	NEAT1	0x0
1093	chr11	65202147	65203375	+	NEAT1	0x0
1094	chr11	65205474	65206618	+	MIR612	0x0
1095	chr11	65211102	65213301	+	MIR612	0x0
1096	chr11	65267086	65272491	+	MALAT1	0x0
1097	chr11	65272670	65273959	+	MALAT1	0x0
1098	chr11	65303924	65305111	+	SCYL1	0x0
1099	chr11	65318518	65319691	−	LTBP3	0x0
1100	chr11	65340337	65341462	+	FAM89B	0x0
1101	chr11	65382895	65384217	+	PCNXL3	0x0
1102	chr11	65403876	65405283	+	PCNXL3	0x0
1103	chr11	65420601	65421743	−	RELA	0x0
1104	chr11	65606663	65607901	+	SNX32	0x0
1105	chr11	65621762	65623097	−	CFL1	0x0
1106	chr11	65657684	65658871	+	CCDC85B	0x0
1107	chr11	65732857	65734198	+	SART1	0x0
1108	chr11	66040462	66041680	+	RAB1B	0x4
1109	chr11	66115021	66116249	+	TMEM151A	0x0
1110	chr11	66412944	66414301	+	RBM14-RBM4	0x0
1111	chr11	66412944	66414301	+	RBM4	0x0
1112	chr11	66458249	66459396	−	SPTBN2	0x0
1113	chr11	66477558	66478690	−	SPTBN2	0x0
1114	chr11	66998612	66999821	+	KDM2A	0x0
1115	chr11	67129304	67130537	+	LOC100130987	0x0
1116	chr11	67171122	67172325	+	PPP1CA	0x1
1117	chr11	67888092	67889195	−	CHKA	0x0
1118	chr11	68114944	68116240	+	LRP5	0x2
1119	chr11	68124695	68125868	+	LRP5	0x2
1120	chr11	68178330	68179614	+	LRP5	0x2
1121	chr11	68380749	68381958	+	PPP6R3	0x0
1122	chr11	68457842	68459072	+	GAL	0x0
1123	chr11	69465610	69466793	+	CCND1	0x2
1124	chr11	69468028	69469207	+	CCND1	0x2
1125	chr11	70260296	70261444	+	CTTN	0x0
1126	chr11	70266096	70267236	+	CTTN	0x0
1127	chr11	70281342	70282887	+	CTTN	0x0
1128	chr11	70487751	70488908	−	SHANK2	0x0
1129	chr11	71719638	71720823	−	NUMA1	0x2
1130	chr11	72396112	72397289	−	ARAP1	0x0
1131	chr11	72465381	72466597	−	STARD10	0x0
1132	chr11	72533951	72535153	+	ATG16L2	0x0
1133	chr11	73089519	73090913	+	RELT	0x0
1134	chr11	73102560	73103766	+	RELT	0x0
1135	chr11	73113207	73114421	−	FAM168A	0x0
1136	chr11	73292950	73294141	−	FAM168A	0x0
1137	chr11	73471139	73472306	−	RA86A	0x0
1138	chr11	73686049	73687204	−	UCP2	0x0
1139	chr11	73692040	73693221	−	UCP2	0x0
1140	chr11	74395754	74397001	+	POLD3	0x0
1141	chr11	74459371	74460563	+	RNF169	0x0
1142	chr11	74548402	74549680	+	RNF169	0x0
1143	chr11	74953752	74954991	+	LOC100507050	0x0
1144	chr11	74973123	74974469	−	ARRB1	0x0
1145	chr11	75114637	75115718	+	RPS3	0x0
1146	chr11	75114637	75115718	+	SNORD15B	0x0
1147	chr11	75116122	75117284	+	RPS3	0x0
1148	chr11	75946310	75947433	−	WNT11	0x1
1149	chr11	76188233	76189474	+	C11orf30	0x2
1150	chr11	77445397	77446524	−	RSF1	0x0
1151	chr11	77596958	77598370	+	C11or167	0x0
1152	chr11	78203348	78204744	−	NARS2	0x0
1153	chr11	78281988	78283213	−	NARS2	0x0
1154	chr11	79158852	79160049	+	USP35	0x0
1155	chr11	82400096	82401484	+	C11orf82	0x0
1156	chr11	85194521	85195729	+	TMEM126B	0x0
1157	chr11	85372133	85373311	−	CREBZF	0x0
1158	chr11	85374978	85376093	−	CREBZF	0x0
1159	chr11	85955600	85956820	+	EED	0x0
1160	chr11	86781990	86783149	+	TMEM135	0x0
1161	chr11	87035894	87037074	+	TMEM135	0x0
1162	chr11	87173935	87175142	+	TMEM135	0x0
1163	chr11	88115883	88117057	+	TYR	0x0
1164	chr11	88601325	88602522	−	GRM5	0x2
1165	chr11	90016508	90017736	+	NAALAD2	0x0
1166	chr11	92628475	92629717	+	FAT3	0x2
1167	chr11	93430080	93431249	+	KIAA1731	0x0
1168	chr11	93431321	93432559	+	KIAA1731	0x0
1169	chr11	93454277	93455631	+	KIAA1731	0x0
1170	chr11	93454277	93455631	+	SCARNA9	0x0
1171	chr11	93463172	93467318	−	MIR1304	0x0
1172	chr11	93463172	93467318	−	SNORA1	0x0
1173	chr11	93463172	93467318	−	SNORA18	0x0
1174	chr11	93463172	93467318	−	SNORA25	0x0
1175	chr11	93463172	93467318	−	SNORA32	0x0
1176	chr11	93463172	93467318	−	SNORA8	0x0
1177	chr11	93463172	93467318	−	SNORD5	0x0
1178	chr11	93463172	93467318	−	SNORD6	0x0
1179	chr11	93467776	93468906	−	SNORA40	0x0
1180	chr11	93471932	93473313	−	TAF1D	0x0
1181	chr11	93710378	93711559	−	VSTM5	0x0
1182	chr11	93951439	93952636	−	GPR83	0x0
1183	chr11	94150949	94152169	−	MRE11A	0x2
1184	chr11	94191674	94192852	−	MRE11A	0x2
1185	chr11	94626721	94627940	+	AMOTL1	0x0
1186	chr11	94901765	94902876	−	SESN3	0x0
1187	chr11	94905459	94906618	−	SESN3	0x0
1188	chr11	95825694	95826915	−	MAML2	0x2
1189	chr11	97636450	97637649	−	CCDC82	0x0
1190	chr11	102165160	102166359	+	BIRC3	0x2
1191	chr11	102267092	102268404	−	TMEM123	0x0
1192	chr11	103002798	103004000	+	DYNC2H1	0x2
1193	chr11	103027441	103028540	+	DYNC2H1	0x2
1194	chr11	103174765	103176006	+	DYNC2H1	0x2
1195	chr11	105633446	105634654	+	GRIA4	0x0
1196	chr11	105968338	105969437	+	AASDHPPT	0x0
1197	chr11	108002424	108003642	+	ACAT1	0x0
1198	chr11	108047167	108048374	−	NPAT	0x0
1199	chr11	108344138	108345359	−	KDELC2	0x0
1200	chr11	108788410	108789619	+	DDX10	0x0
1201	chr11	110100605	110101959	−	RDX	0x0
1202	chr11	110165437	110166631	−	RDX	0x0
1203	chr11	111611018	111612348	−	PPP2R1B	0x1
1204	chr11	111630786	111631964	−	PPP2R1B	0x1
1205	chr11	111692090	111693298	−	ALG9	0x0
1206	chr11	111911615	111912858	+	DLAT	0x0
1207	chr11	113692674	113693849	−	USP28	0x2
1208	chr11	113737800	113739046	+	HTR3B	0x0
1209	chr11	114293964	114295180	+	RBM7	0x0
1210	chr11	115046086	115047511	−	CADM1	0x1
1211	chr11	115148719	115149902	−	CADM1	0x1
1212	chr11	115342456	115343604	−	CADM1	0x1
1213	chr11	115471774	115472976	+	FAM55B	0x0
1214	chr11	115692620	115693820	−	APOC3	0x0
1215	chr11	117708156	117709359	−	FXYD6	0x0
1216	chr11	118279246	118280394	+	ATP5L	0x0
1217	chr11	118342606	118343847	+	MLL	0x2
1218	chr11	118393102	118394257	+	MLL	0x2
1219	chr11	118427130	118428283	−	IFT46	0x0
1220	chr11	118470924	118472083	+	ARCN1	0x0
1221	chr11	118527620	118528782	+	PHLDB1	0x0
1222	chr11	118619817	118620995	−	DDX6	0x0
1223	chr11	118894521	118895926	−	SLC37A4	0x0
1224	chr11	118914425	118916307	−	HYOU1	0x0
1225	chr11	118964055	118965438	−	H2AFX	0x0
1226	chr11	120219784	120220989	+	ARHGEF12	0x1
1227	chr11	120346835	120347953	+	ARHGEF12	0x1
1228	chr11	120356530	120357629	+	ARHGEF12	0x1
1229	chr11	120901672	120902820	−	TBCEL	0x0
1230	chr11	122928226	122929337	−	HSPA8	0x0
1231	chr11	122929463	122930664	−	HSPA8	0x0
1232	chr11	123050799	123052002	−	CLMP	0x0
1233	chr11	123595631	123596826	−	ZNF202	0x0
1234	chr11	123634095	123635377	+	GRAMD1B	0x0
1235	chr11	124505785	124507034	+	TBRG1	0x1
1236	chr11	124923736	124924915	−	TMEM218	0x0
1237	chr11	125169906	125171066	+	PKNOX2	0x0
1238	chr11	125453376	125454570	+	EI24	0x1
1239	chr11	125490149	125491346	+	STT3A	0x0
1240	chr11	125547115	125548337	+	CHEK1	0x1
1241	chr11	126076638	126077817	−	RPUSD4	0x0
1242	chr11	126147179	126148335	+	FOXRED1	0x0
1243	chr11	129297040	129298265	+	BARX2	0x0
1244	chr11	130013182	130015087	+	APLP2	0x0
1245	chr11	133768160	133769577	−	LOC283174	0x0
1246	chr11	133768160	133769577	−	MIR4697	0x0
1247	chr11	133775128	133776296	−	LOC283174	0x0
1248	chr11	133801584	133802941	−	IGSF9B	0x0
1249	chr11	133905644	133907090	−	IGSF9B	0x0
1250	chr11	134207878	134209110	+	GLB1L2	0x0
1251	chr11	134244503	134245731	+	GLB1L2	0x0
1252	chr12	364481	365671	−	SLC6A13	0x0
1253	chr12	392498	393756	−	KDMSA	0x2
1254	chr12	413102	414299	+	CCDC77	0x0
1255	chr12	973775	975079	+	WNK1	0x0
1256	chr12	1038335	1039518	−	RAD52	0x0
1257	chr12	1136736	1137951	+	ERC1	0x2
1258	chr12	2364481	2365782	+	CACNA1C	0x0
1259	chr12	2675917	2677086	+	CACNA1C	0x0
1260	chr12	2912189	2913544	+	FKBP4	0x0
1261	chr12	2927125	2928323	+	ITFG2	0x0
1262	chr12	2986248	2987433	+	C12orf32	0x0
1263	chr12	2997913	2999053	+	C12orf32	0x0
1264	chr12	3008519	3009671	+	TULP3	0x0
1265	chr12	3079751	3080900	+	TEAD4	0x0
1266	chr12	3153592	3154803	+	TEAD4	0x0
1267	chr12	4399756	4400906	+	CCND2	0x2
1268	chr12	4411084	4412957	+	CCND2	0x2
1269	chr12	4772532	4773729	+	NDUFA9	0x0
1270	chr12	6618969	6620370	+	NCAPD2	0x0
1271	chr12	6618969	6620370	+	SCARNA10	0x0
1272	chr12	6626244	6627393	+	NCAPD2	0x0
1273	chr12	6646283	6647637	+	GAPDH	0x0
1274	chr12	6652008	6653217	−	IFFO1	0x0
1275	chr12	6678923	6680015	−	CHD4	0x2
1276	chr12	6690067	6691369	−	CHD4	0x2
1277	chr12	6690067	6691369	−	SCARNA11	0x0
1278	chr12	6709165	6710346	−	CHD4	0x2
1279	chr12	6775774	6776986	−	ZNF384	0x2
1280	chr12	6879192	6880496	+	PTMS	0x2
1281	chr12	7052424	7053623	+	C12orf57	0x0
1282	chr12	7074110	7075210	−	PHB2	0x0
1283	chr12	7076077	7077300	−	PHB2	0x0
1284	chr12	7076077	7077300	−	SCARNA12	0x0
1285	chr12	7079104	7080280	−	PHB2	0x0
1286	chr12	7362702	7363899	+	PEX5	0x0
1287	chr12	9451079	9452259	+	LOC642846	0x0
1288	chr12	9572828	9574121	−	DDX12P	0x0
1289	chr12	10865278	10866425	−	CSDA	0x0
1290	chr12	11283034	11284164	−	TAS2R30	0x0
1291	chr12	12396929	12398082	−	LRP6	0x0
1292	chr12	12693877	12695074	−	DUSP16	0x0
1293	chr12	12843359	12844568	+	CDKN1B	0x2
1294	chr12	12882447	12883597	+	APOLD1	0x0
1295	chr12	13349667	13350884	+	EMP1	0x1
1296	chr12	14553333	14554482	+	ATF7IP	0x0
1297	chr12	14576917	14578148	+	ATF7IP	0x0
1298	chr12	16034899	16035998	+	STRAP	0x0
1299	chr12	19459402	19460532	+	PLEKHA5	0x0
1300	chr12	19609180	19610356	−	PLCZ1	0x0
1301	chr12	19646275	19647461	+	AEBP2	0x0
1302	chr12	19667021	19668250	+	AEBP2	0x0
1303	chr12	19787207	19788406	+	AEBP2	0x0
1304	chr12	20703858	20705060	+	PDE3A	0x0
1305	chr12	21787731	21789097	−	LDHB	0x0
1306	chr12	21796330	21797498	−	LDHB	0x0
1307	chr12	21806910	21808112	−	LDHB	0x0
1308	chr12	22841550	22842755	−	ETNK1	0x0
1309	chr12	24302800	24303994	−	SOX5	0x2
1310	chr12	25359335	25360441	−	KRAS	0x2
1311	chr12	26799681	26800860	−	ITPR2	0x0
1312	chr11	27182459	27183558	+	MED21	0x0
1313	chr12	28416937	28418091	+	CCDC91	0x0
1314	chr12	29318753	29320044	+	FAR2	0x0
1315	chr12	31255183	31256382	+	DDX11	0x2
1316	chr12	32329775	32330974	+	BICD1	0x0
1317	chr12	34358128	34359328	+	ALG10	0x0
1318	chr12	38554688	38555905	−	CPNE8	0x0
1319	chr12	38556667	38557854	−	CPNE8	0x0
1320	chr12	40306319	40307450	−	SLC2A13	0x2
1321	chr12	41291889	41293092	+	CNTN1	0x2
1322	chr12	42802927	42804130	+	PPHLN1	0x0
1323	chr12	44112475	44113668	−	PUS7L	0x0
1324	chr11	46210804	46211974	−	ARID2	0x1
1325	chr12	46348079	46349248	−	SCAF11	0x0
1326	chr12	46578570	46579679	−	SLC38A1	0x0
1327	chr12	46580852	46583054	−	SLC38A1	0x0
1328	chr12	46662262	46663408	−	SLC38A1	0x0
1329	chr12	46753993	46755126	−	SLC38A2	0x0
1330	chr12	47028778	47029926	+	MIR4698	0x0
1331	chr12	48211842	48213021	−	HDAC7	0x0
1332	chr12	48361676	48362943	+	TMEM106C	0x0
1333	chr12	48929861	48931073	−	LALBA	0x0
1334	chr11	49047617	49048857	−	KANSL2	0x0
1335	chr12	49047617	49048857	−	MIR1291	0x0
1336	chr12	49047617	49048857	−	SNORA34	0x0
1337	chr12	49049902	49051113	−	SNORA2A	0x0
1338	chr12	49053651	49054832	−	KANSL2	0x0
1339	chr12	49318110	49319282	−	FKBP11	0x0
1340	chr12	49329445	49332620	−	ARF3	0x0
1341	chr12	49414410	49415621	−	MLL2	0x2
1342	chr12	49435603	49436758	−	MLL2	0x2
1343	chr12	49529532	49530765	+	TUBA1C	0x0
1344	chr12	49548759	49550000	+	TUBA1C	0x0
1345	chr12	49666456	49667619	+	TUBA1C	0x0
1346	chr12	49920100	49921328	+	SPATS2	0x0
1347	chr12	49985589	49986795	+	PRPF40B	0x0
1348	chr12	50128781	50130000	−	FMNL3	0x2
1349	chr12	50134767	50135968	+	TMBIM6	0x0
1350	chr12	50145699	50146862	+	TMBIM6	0x0
1351	chr12	50156264	50157519	+	TMBIM6	0x0
1352	chr12	50157722	50158819	+	TMBIM6	0x0
1353	chr12	50184490	50185694	−	NCKAP5L	0x0
1354	chr12	50491552	50492780	+	SMARCD1	0x2
1355	chr12	50849813	50851143	+	LARP4	0x0
1356	chr12	51090319	51091513	+	DIP28	0x0
1357	chr12	51498676	51499900	−	TFCP2	0x0
1358	chr12	51634102	51635201	+	DAZAP2	0x0
1359	chr12	51636316	51637386	+	DAZAP2	0x0
1360	chr12	52401840	52403056	+	GRASP	0x0
1361	chr12	53415744	53416893	+	EIF4B	0x0
1362	chr12	53427832	53429067	+	EIF4B	0x0
1363	chr12	53434475	53435740	+	EIF4B	0x0
1364	chr12	53440754	53442110	−	LOC283335	0x0
1365	chr12	53677339	53678467	+	ESPL1	0x2
1366	chr12	53861998	53863198	+	PCBP2	0x0
1367	chr12	53872702	53873900	+	PCBP2	0x0
1368	chr12	53925841	53927016	−	ATF7	0x0
1369	chr12	53959188	53960365	−	ATF7	0x0
1370	chr12	54058406	54059659	−	ATP5G2	0x0
1371	chr12	54105636	54106848	−	CALCOCO1	0x0
1372	chr12	54116856	54118029	−	CALCOCO1	0x0
1373	chr12	54624276	54625822	−	CBX5	0x0
1374	chr12	54624276	54625822	−	MIR3198-2	0x0
1375	chr12	54626334	54627796	−	CBX5	0x0
1376	chr12	54632554	54633647	−	CBX5	0x0
1377	chr12	54678040	54679244	+	HNRNPA1	0x0
1378	chr12	54678040	54679244	+	HNRNPA1P10	0x0
1379	chr12	54680244	54681745	+	HNRNPA1	0x0
1380	chr12	54744020	54745227	+	COPZ1	0x0
1381	chr12	56144734	56145888	+	GDF11	0x0
1382	chr12	56214650	56215827	−	DNAJC14	0x0
1383	chr12	56319123	56320301	−	WIBG	0x0
1384	chr12	56509912	56511132	+	RPL41	0x0
1385	chr12	56529980	56531185	+	ESYT1	0x0
1386	chr12	56554648	56555864	+	MYL6	0x0
1387	chr12	56567925	56569100	−	SMARCC2	0x0
1388	chr12	56574409	56575535	−	SMARCC2	0x0
1389	chr12	56631521	56633609	−	ANKRD52	0x0
1390	chr12	56650675	56651839	−	ANKRD52	0x0
1391	chr12	56665418	56666553	−	CS	0x0
1392	chr12	56669294	56670401	−	CS	0x0
1393	chr12	56904854	56906036	+	RBMS2	0x0
1394	chr12	56983285	56984504	+	RBMS2	0x0
1395	chr12	56990790	56991985	−	BAZ2A	0x0
1396	chr12	56998428	56999593	−	BAZ2A	0x0
1397	chr12	57031567	57032662	−	ATP5B	0x0
1398	chr12	57038251	57039453	−	ATP5B	0x0
1399	chr12	57038251	57039453	−	SNORD59A	0x0
1400	chr12	57057255	57058446	−	PTGES3	0x0
1401	chr12	57106012	57107208	−	NACA	0x2
1402	chr12	57452030	57453472	−	TMEM194A	0x0
1403	chr12	57557543	57558713	+	LRP1	0x0
1404	chr12	57650492	57651591	−	R3HDM2	0x0
1405	chr12	57677230	57678420	−	R3HDM2	0x0
1406	chr12	57764748	57765913	−	R3HDM2	0x0
1407	chr12	57923781	57924975	−	DCTN2	0x0
1408	chr12	57998635	57999786	+	DTX3	0x0
1409	chr12	59270638	59271817	−	LRIG3	0x1
1410	chr12	62948534	62949723	−	MON2	0x0
1411	chr12	63327834	63329011	−	PPM1H	0x0
1412	chr12	63358577	63359800	+	MIRLET7I	0x1
1413	chr12	65603419	65604657	−	LEMD3	0x0
1414	chr12	67285540	67286640	−	GRIP1	0x0
1415	chr12	67296512	67297691	−	GRIP1	0x0
1416	chr12	67431752	67432968	−	GRIP1	0x0
1417	chr12	67698510	67699685	+	CAND1	0x0
1418	chr12	69005201	69006430	+	RAP1B	0x0
1419	chr12	69649981	69651119	+	CPSF6	0x0
1420	chr12	69994544	69995776	+	CCT2	0x0
1421	chr12	70194830	70196046	+	RAB3IP	0x0
1422	chr12	70679838	70681070	+	CNOT2	0x0
1423	chr12	71896974	71898191	+	LGR5	0x0
1424	chr11	72004583	72005719	−	ZFC3H1	0x0
1425	chr12	72005992	72007142	−	ZFC3H1	0x0
1426	chr12	72180935	72182073	+	RAB21	0x0
1427	chr12	74850635	74851794	+	ATXN7L3B	0x0
1428	chr12	75679900	75681078	−	CAPS2	0x0
1429	chr12	75891366	75892543	+	GLIPR1	0x1
1430	chr12	75892900	75894150	−	KRR1	0x0
1431	chr12	76430189	76431289	−	PHLDA1	0x0
1432	chr12	76439331	76440505	−	NAP1L1	0x0
1433	chr12	76443863	76444966	−	NAP1L1	0x0
1434	chr12	76451371	76460500	−	NAP1L1	0x0
1435	chr12	76461818	76462967	−	NAP1L1	0x0
1436	chr12	77224354	77225520	+	ZDHHC17	0x1
1437	chr12	77423288	77424487	−	E2F7	0x4
1438	chr12	79454116	79455268	−	PAWR	0x1
1439	chr12	79545435	79546544	−	PAWR	0x1
1440	chr12	80065464	80066629	−	PAWR	0x1
1441	chr12	81938745	81939922	−	PPFIA2	0x0
1442	chr12	82111266	82112433	−	PPFIA2	0x0
1443	chr12	82763997	82765204	+	C12orf26	0x0
1444	chr12	83250305	83251851	+	TMTC2	0x0
1445	chr12	83445406	83446612	+	TMTC2	0x0
1446	chr12	85275664	85276792	−	SLC6A15	0x2
1447	chr12	85689617	85690718	+	ALX1	0x0
1448	chr12	88478022	88479168	−	CEP290	0x0
1449	chr12	88823643	88824885	+	TMTC3	0x0
1450	chr12	89912721	89913853	−	GALNT4	0x0
1451	chr12	89912721	89913853	−	POC1B-GALNT4	0x0
1452	chr12	90013416	90014561	−	ATP2B1	0x0
1453	chr12	90082996	90084168	−	ATP2B1	0x0
1454	chr12	92120144	92121361	+	CLLU1	0x0
1455	chr12	92734804	92736003	+	CLLU1	0x0
1456	chr12	93795485	93796681	+	NUDT4	0x0
1457	chr12	93795485	93796681	+	NUDT4P1	0x0
1458	chr12	93801835	93803801	−	UBE2N	0x0
1459	chr12	93895618	93896756	+	MRPL42	0x0
1460	chr12	93898154	93899253	+	MRPL42	0x0
1461	chr12	93902860	93904057	+	MRPL42	0x0
1462	chr12	94033987	94035163	−	LOC144481	0x0
1463	chr12	94270786	94271995	+	CRADD	0x0
1464	chr12	95449301	95450478	−	NR2C1	0x0
1465	chr12	95694283	95695450	+	VEZT	0x0
1466	chr12	95838385	95839584	−	USP44	0x0
1467	chr12	95907272	95908503	+	METAP2	0x2
1468	chr12	95945210	95946388	−	USP44	0x0
1469	chr12	96131748	96132931	−	NTN4	0x0
1470	chr12	96679370	96680544	−	CDK17	0x0
1471	chr12	98896705	98897950	+	TMPO	0x0
1472	chr12	98909061	98910417	+	TMPO	0x0
1473	chr12	98928615	98929958	+	TMPO	0x0
1474	chr12	98988112	98989361	+	SLC25A3	0x0
1475	chr12	98992887	98994230	+	SLC25A3	0x0
1476	chr12	98992887	98994230	+	SNORA53	0x0
1477	chr12	99477048	99478198	−	ANKS1B	0x0
1478	chr12	100497710	100498916	−	UHRF1BP1L	0x0
1479	chr12	100562243	100563428	−	GOLGA2P5	0x0
1480	chr12	100672654	100673917	+	SCYL2	0x0
1481	chr12	102599508	102600903	+	PARPBP	0x0
1482	chr12	102606561	102607720	−	PARPBP	0x0
1483	chr12	102819646	102820849	−	IGF1	0x0
1484	chr12	104167901	104169068	−	NTSDCS	0x0
1485	chr12	104324745	104325987	+	HSP90B1	0x0
1486	chr12	104381637	104382863	+	TDG	0x2
1487	chr12	104658682	104659889	+	TXNRD1	0x0
1488	chr12	104714376	104715825	+	TXNRD1	0x0
1489	chr12	104732514	104733718	+	TXNRD1	0x0
1490	chr12	104742733	104744033	+	TXNRD1	0x0
1491	chr12	105283361	105284557	+	C12orf45	0x0
1492	chr12	105392116	105393273	+	C12orf45	0x0
1493	chr12	105397776	105398870	+	C12orf45	0x0
1494	chr12	105503187	105504415	+	KIAA1033	0x0
1495	chr12	106631295	106632921	−	CKAP4	0x0
1496	chr12	106872290	106873478	+	POLR3B	0x0
1497	chr12	107347778	107348955	−	MTERFD3	0x0
1498	chr12	107384669	107385818	−	CRY1	0x0
1499	chr12	107951247	107952444	−	BTBD11	0x0
1500	chr12	108917140	108918239	−	SART3	0x0
1501	chr12	108953954	108955214	−	SART3	0x0
1502	chr12	109038635	109040230	−	CORO1C	0x0
1503	chr12	109312158	109313375	+	DAO	0x0
1504	chr12	109636634	109637824	+	ACACB	0x0
1505	chr12	109724629	109725961	−	FOXN4	0x0
1506	chr12	109740686	109741911	−	FOXN4	0x0
1507	chr12	109761616	109762830	+	ACACB	0x0
1508	chr12	109973462	109974663	+	UBE3B	0x0
1509	chr12	109994373	109995568	−	MMAB	0x0
1510	chr12	110763655	110764854	+	ATP2A2	0x2
1511	chr12	110777915	110779112	+	ATP2A2	0x2
1512	chr12	110783912	110785278	+	ATP2A2	0x2
1513	chr12	110824490	110826195	−	ANAPC7	0x0
1514	chr12	111157924	111159308	−	PPP1CC	0x0
1515	chr12	111855661	111856775	+	SH2B3	0x0
1516	chr12	111948470	111949661	−	ATXN2	0x0
1517	chr12	111958175	111959274	−	ATXN2	0x0
1518	chr12	112460151	112461345	+	ERP29	0x0
1519	chr12	112466354	112467513	−	NAA25	0x0
1520	chr12	112467833	112468970	−	NAA25	0x0
1521	chr12	112504368	112505565	−	NAA25	0x0
1522	chr12	112510461	112511674	−	NAA25	0x0
1523	chr12	112637375	112638555	−	C12orf51	0x2
1524	chr12	112704325	112705613	+	TRAFD1	0x0
1525	chr12	112746050	112747202	−	C12orf51	0x2
1526	chr12	112911069	112912282	+	PTPN11	0x2
1527	chr12	112944565	112946176	+	PTPN11	0x2
1528	chr12	113673828	113675053	+	TPCN1	0x0
1529	chr12	113735248	113736378	+	TPCN1	0x0
1530	chr12	113874548	113875949	+	SDSL	0x0
1531	chr12	115129856	115131062	+	LOC255480	0x0
1532	chr12	116398477	116399619	−	MED13L	0x0
1533	chr12	116433823	116435006	−	MED13L	0x0
1534	chr12	117152663	117154080	−	C12orf49	0x0
1535	chr12	117365284	117366523	+	FBXW8	0x0
1536	chr12	118683520	118685251	+	PEBP1	0x0
1537	chr12	119266964	119268147	+	SRRM4	0x0
1538	chr12	120123558	120130500	−	CIT	0x2
1539	chr12	120574832	120576057	−	GCN1L1	0x0
1540	chr12	120592597	120594106	−	GCN1L1	0x0
1541	chr12	120592597	120594106	−	MIR4498	0x0
1542	chr12	120600352	120601529	−	GCN1L1	0x0
1543	chr12	120636369	120637807	−	RPLPO	0x0
1544	chr12	120659813	120661023	−	PXN	0x0
1545	chr12	120719700	120720918	+	S1RT4	0x0
1546	chr12	120729010	120730242	−	PXN	0x0
1547	chr12	120730321	120731569	−	PXN	0x0
1548	chr12	120779154	120780474	−	MSI1	0x0
1549	chr12	120875360	120876560	+	COX6A1	0x0
1550	chr12	120877815	120879006	+	COX6A1	0x0
1551	chr12	120884509	120885705	+	GATC	0x0
1552	chr12	120935439	120936770	+	DYNLL1	0x0
1553	chr12	121124410	121125575	+	MLEC	0x0
1554	chr12	121138015	121139114	+	MLEC	0x0
1555	chr12	121159111	121160851	+	UNC119B	0x0
1556	chr12	121201895	121203019	−	SPPL3	0x0
1557	chr12	121308258	121309467	−	SPPL3	0x0
1558	chr12	121314068	121315243	−	SPPL3	0x0
1559	chr12	121676294	121677456	−	CAMKK2	0x0
1560	chr12	122496860	122497973	+	BCL7A	0x2
1561	chr12	122627621	122628772	+	MLXIP	0x0
1562	chr12	122779092	122780309	−	CLIP1	0x2
1563	chr12	122825134	122826272	−	CLIP1	0x2
1564	chr12	123120516	123121672	+	KNTC1	0x0
1565	chr12	123444050	123445230	−	ABCB9	0x0
1566	chr12	123745288	123746440	−	CDK2AP1	0x1
1567	chr12	123801208	123802366	−	SBNO1	0x0
1568	chr12	123943066	123944289	+	SNRNP35	0x0
1569	chr12	124081212	124082349	+	TMED2	0x0
1570	chr12	124100782	124101965	+	DDX55	0x0
1571	chr12	124145169	124146424	+	GTF2H3	0x0
1572	chr12	124219151	124220344	+	ATP6V0A2	0x0
1573	chr12	124854201	124855376	−	NCOR2	0x0
1574	chr12	124903987	124905161	−	NCOR2	0x0
1575	chr12	124915360	124916735	−	NCOR2	0x0
1576	chr12	124922826	124924510	−	NCOR2	0x0
1577	chr12	124979296	124980474	−	NCOR2	0x0
1578	chr12	125261806	125262989	−	SCARB1	0x0
1579	chr12	125339397	125340559	−	SCARB1	0x0
1580	chr12	125397675	125398874	−	UBC	0x0
1581	chr12	127649925	127651531	−	LOC440117	0x0
1582	chr12	131358620	131359786	+	RAN	0x0
1583	chr12	131359882	131362107	+	RAN	0x0
1584	chr12	132589229	132590362	+	EP400NL	0x0
1585	chr12	132638091	132639288	+	NOC4L	0x0
1586	chr12	133159939	133161159	+	FBRSL1	0x4
1587	chr12	133235503	133236603	−	POLE	0x0
1588	chr12	133249065	133250242	−	POLE	0x0
1589	chr12	133286628	133287809	+	PGAM5	0x0
1590	chr12	133297027	133298212	+	PGAM5	0x0
1591	chr12	133302273	133303436	−	ANKLE2	0x0
1592	chr12	133340445	133341593	+	PGAM5	0x0
1593	chr12	133346386	133347715	−	GOLGA3	0x0
1594	chr12	133401746	133403135	+	PGAM5	0x0
1595	chr13	20182187	20183387	+	MPHOSPH8	0x0
1596	chr13	20198790	20199958	+	MPHOSPH8	0x0
1597	chr13	21185776	21187001	+	IFT88	0x1
1598	chr13	21535345	21536549	+	SAP18	0x0
1599	chr13	21946854	21948041	−	ZDHHC20	0x0
1600	chr13	21948636	21949812	−	ZDHHC20	0x0
1601	chr13	21994684	21995835	−	ZDHHC20	0x0
1602	chr13	23903680	23904855	−	SACS	0x0
1603	chr13	23934784	23935912	−	SACS	0x0
1604	chr13	24434695	24435873	−	MIPEP	0x0
1605	chr13	24699699	24700878	−	C1QTNF9B	0x0
1606	chr13	24796585	24798913	+	SPATA13	0x2
1607	chr13	25470098	25471258	−	CENPJ	0x0
1608	chr13	25670480	25671744	+	PABPC3	0x2
1609	chr13	26853541	26854689	+	CDK8	0x0
1610	chr13	26936737	26937942	+	CDK8	0x0
1611	chr13	27694168	27695357	−	USP12	0x0
1612	chr13	27827796	27830192	+	RPL21	0x0
1613	chr13	27827796	27830192	+	RPL21P28	0x0
1614	chr13	27827796	27830192	+	SNORA27	0x0
1615	chr13	27827796	27830192	+	SNORD102	0x0
1616	chr13	28007054	28008244	+	GTF3A	0x0
1617	chr13	28563055	28564262	−	PRHOXNB	0x0
1618	chr13	28712198	28713431	+	PAN3	0x0
1619	chr13	30085991	30087580	−	SLC7A1	0x0
1620	chr13	30106461	30107604	−	SLC7A1	0x0
1621	chr13	30109547	30110829	−	SLC7A1	0x0
1622	chr13	30814590	30815735	−	KATNAL1	0x0
1623	chr13	31712045	31713225	−	HSPH1	0x0
1624	chr13	34410120	34411619	+	RFC3	0x0
1625	chr13	34497437	34498845	+	RFCS	0x0
1626	chr13	34526824	34527999	+	RFCS	0x0
1627	chr13	35939677	35940865	+	NBEA	0x0
1628	chr13	37427215	37428396	−	SMAD9	0x0
1629	chr13	37439099	37440278	−	SMAD9	0x0
1630	chr13	41132450	41133622	−	FOXO1	0x1
1631	chr13	41155039	41156154	−	FOXO1	0x1
1632	chr13	41494897	41496052	−	LOC100616668	0x0
1633	chr13	41494897	41496052	−	SUGT1P3	0x0
1634	chr13	42352226	42353364	−	KIAA0564	0x0
1635	chr13	42439523	42440727	−	KIAA0564	0x0
1636	chr13	42893974	42895101	+	AKAP11	0x2
1637	chr13	44168571	44169757	−	ENOX1	0x0
1638	chr13	45575759	45576957	+	KIAA1704	0x0
1639	chr13	45825141	45826367	+	GTF2F2	0x0
1640	chr13	45910549	45912314	−	SNORA31	0x0
1641	chr13	45910549	45912314	−	TPT1	0x0
1642	chr13	46948034	46949263	−	KIAA0226L	0x0
1643	chr13	49561491	49562687	+	FNDC3A	0x0
1644	chr13	50587746	50588962	−	DLEU2	0x1
1645	chr13	50656526	50657696	+	DLEU1	0x1
1646	chr13	51323418	51324638	+	RNASEH2B	0x0
1647	chr13	51837909	51839104	+	FAM124A	0x0
1648	chr13	52987379	52988940	−	VPS36	0x0
1649	chr13	53190495	53191693	+	HNRNPA1L2	0x0
1650	chr13	60651419	60652765	−	DIAPH3	0x0
1651	chr13	61015885	61017092	+	TDRD3	0x0
1652	chr13	61125023	61126193	+	TDRD3	0x0
1653	chr13	61363164	61364351	+	TDRD3	0x0
1654	chr13	67840715	67841891	−	PCDH9	0x0
1655	chr13	72228968	72230115	−	DACH1	0x0
1656	chr13	72252217	72253358	−	DACH1	0x0
1657	chr13	72388884	72389994	−	DACH1	0x0
1658	chr13	72419172	72420352	−	DACH1	0x0
1659	chr13	73282402	73283576	−	MZT1	0x0
1660	chr13	73301105	73302258	−	MZT1	0x0
1661	chr13	73308096	73309322	+	BORA	0x0
1662	chr13	74505335	74506483	−	KLF12	0x0
1663	chr13	75883686	75884853	−	TBC1D4	0x0
1664	chr13	75935627	75936804	−	TBC1D4	0x0
1665	chr13	76134337	76135485	+	UCHL3	0x0
1666	chr13	76142156	76143379	+	UCHL3	0x0
1667	chr13	76179345	76180503	+	UCHL3	0x0
1668	chr13	76791681	76792834	+	LMO7	0x2
1669	chr13	77459623	77460867	−	KCTD12	0x0
1670	chr13	77581326	77582522	−	FBXL3	0x0
1671	chr13	77592190	77593366	−	FBXL3	0x0
1672	chr13	77730560	77731688	−	MYCBP2	0x2
1673	chr13	79176171	79177675	−	POU4F1	0x0
1674	chr13	79188083	79189266	−	RNF219	0x0
1675	chr13	79888041	79889331	−	RBM26	0x0
1676	chr13	79939705	79940928	−	RBM26	0x0
1677	chr13	80071204	80072474	+	NDFIP2	0x0
1678	chr13	92252899	92254129	+	GPC5	0x0
1679	chr13	95840472	95841650	−	ABCC4	0x0
1680	chr13	95868999	95870171	−	ABCC4	0x0
1681	chr13	96293455	96294610	−	DZIP1	0x0
1682	chr13	96855475	96856610	+	HS6ST3	0x0
1683	chr13	97601125	97602326	−	OXGR1	0x0
1684	chr13	98652227	98653437	+	IPO5	0x0
1685	chr13	99104245	99105441	−	STK24	0x0
1686	chr13	99205745	99206936	−	STK24	0x0
1687	chr13	99323732	99324883	+	FARP1	0x0
1688	chr13	99857416	99858783	+	UBAC2	0x0
1689	chr13	99866861	99868315	−	MIR548AN	0x0
1690	chr13	102651242	102652440	+	ITGBL1	0x0
1691	chr13	103278915	103280017	−	TPP2	0x0
1692	chr13	103355620	103356795	−	METTL21C	0x0
1693	chr13	107210710	107211839	−	ARGLU1	0x0
1694	chr13	108076427	108077608	−	FAM155A	0x0
1695	chr13	108161143	108162342	−	FAM155A	0x0
1696	chr13	108264790	108265967	−	FAM155A	0x0
1697	chr13	108299224	108300407	−	FAM155A	0x0
1698	chr13	109513961	109515157	−	LIG4	0x0
1699	chr13	110435906	110437076	−	IRS2	0x0
1700	chr13	110566925	110568267	+	COL4A2	0x2
1701	chr13	111348428	111349606	−	CARS2	0x0
1702	chr13	113598283	113599440	−	MCF2L-AS1	0x0
1703	chr13	113833527	113834684	−	PCID2	0x0
1704	chr13	113917507	113918650	+	CUL4A	0x1
1705	chr13	113931038	113932264	+	CUL4A	0x1
1706	chr13	114183681	114184915	+	TMCO3	0x0
1707	chr13	114294691	114295879	+	TFDP1	0x0
1708	chr14	20742356	20743528	−	TTC5	0x0
1709	chr14	20790801	20792085	−	CCNB1IP1	0x0
1710	chr14	20810712	20812122	−	RPPH1	0x0
1711	chr14	20882556	20883783	+	APEX1	0x0
1712	chr14	21081438	21082537	−	RNASE12	0x0
1713	chr14	21100650	21101887	+	ANG	0x0
1714	chr14	21120694	21121938	−	OR6S1	0x0
1715	chr14	21127573	21128700	−	OR6S1	0x0
1716	chr14	21130773	21132001	−	OR6S1	0x0
1717	chr14	21149336	21150513	+	ANG	0x0
1718	chr14	21150862	21152183	+	ANG	0x0
1719	chr14	21701758	21702922	−	HNRNPC	0x0
1720	chr14	21819168	21820374	−	SUPT16H	0x0
1721	chr14	21883441	21884661	−	CHD8	0x0
1722	chr14	21927022	21928341	−	RAB2B	0x0
1723	chr14	21970840	21972169	−	METTL3	0x2
1724	chr14	23398370	23399587	+	REM2	0x0
1725	chr14	23534766	23535940	−	ACIN1	0x2
1726	chr14	23539764	23541105	−	ACIN1	0x2
1727	chr14	23794361	23795539	+	BCL2L2-PABPN1	0x0
1728	chr14	23794361	23795539	+	PABPN1	0x0
1729	chr14	23947343	23948545	+	NGDN	0x0
1730	chr14	24736302	24737477	−	RABGGTA	0x0
1731	chr14	24783279	24784402	+	LTB4R	0x0
1732	chr14	24842532	24843745	+	NFATC4	0x0
1733	chr14	24910543	24911763	−	SDR39U1	0x0
1734	chr14	26150011	26151194	−	5TXBP6	0x0
1735	chr14	28733778	28735048	+	FOXG1	0x4
1736	chr14	30270786	30271961	−	PRKD1	0x2
1737	chr14	31070268	31071668	+	G2E3	0x0
1738	chr14	31481080	31482291	−	MIR624	0x0
1739	chr14	31585380	31586544	−	HECTD1	0x0
1740	chr14	31919046	31920232	−	C14orf126	0x0
1741	chr14	32589428	32590647	+	ARHGAP5	0x0
1742	chr14	32803437	32804634	+	AKAP6	0x2
1743	chr14	32853729	32854962	+	AKAP6	0x2
1744	chr14	34929007	34930135	−	SPTSSA	0x0
1745	chr14	35328000	35329104	+	BAZ1A	0x0
1746	chr14	35857231	35858622	−	NFKBIA	0x2
1747	chr14	36231437	36232687	−	RALGAPA1	0x0
1748	chr14	39455981	39457143	+	GEMIN2	0x0
1749	chr14	39617080	39618404	−	TRAPPC6B	0x0
1750	chr14	39650236	39651971	+	PNN	0x1
1751	chr14	39837183	39838385	+	CTAGE5	0x0
1752	chr14	44660534	44661689	−	FSCB	0x0
1753	chr14	45429705	45430918	−	KLHL28	0x0
1754	chr14	45513128	45514344	+	FAM179B	0x0
1755	chr14	45571192	45572327	+	PRPF39	0x0
1756	chr14	45669258	45670454	+	FANCM	0x2
1757	chr14	45860772	45861964	+	FANCM	0x2
1758	chr14	50052744	50054179	+	LRR1	0x0
1759	chr14	50072238	50073452	+	LRR1	0x0
1760	chr14	50252419	50253619	−	NEMF	0x0
1761	chr14	50283121	50284320	−	NEMF	0x0
1762	chr14	50319903	50321149	−	NEMF	0x0
1763	chr14	50328727	50329939	−	NEMF	0x0
1764	chr14	50534715	50536100	+	ARF6	0x0
1765	chr14	50867418	50868611	−	CDKL1	0x0
1766	chr14	51255767	51256946	−	NIN	0x2
1767	chr14	51464045	51465182	−	TRIM9	0x0
1768	chr14	51574132	51575351	+	TMX1	0x0
1769	chr14	51712422	51713625	+	TMX1	0x0
1770	chr14	51715602	51716791	+	TMX1	0x0
1771	chr14	51721809	51723001	+	TMX1	0x0
1772	chr14	53010501	53011643	−	TXNDC16	0x0
1773	chr14	53052610	53053853	+	GPR137C	0x0
1774	chr14	53084258	53085453	+	GPR137C	0x0
1775	chr14	53517339	53518466	−	DDHD1	0x0
1776	chr14	54893869	54895013	−	CNIH	0x0
1777	chr14	55119067	55120298	+	SAMD4A	0x0
1778	chr14	56166774	56167972	+	KTN1	0x2
1779	chr14	57746954	57748160	+	MUDENG	0x0
1780	chr14	58645963	58647181	+	ACTR10	0x0
1781	chr14	58706021	58707218	−	FLJ31306	0x0
1782	chr14	60582184	60583444	+	C14orf135	0x0
1783	chr14	60590498	60591850	+	C14orf135	0x0
1784	chr14	60715423	60716633	+	PPM1A	0x0
1785	chr14	60728399	60729605	+	PPM1A	0x0
1786	chr14	63589788	63590983	+	RHOJ	0x0
1787	chr14	64481686	64482836	+	SYNE2	0x0
1788	chr14	64595923	64597126	+	SYNE2	0x0
1789	chr14	64640181	64641308	+	SYNE2	0x0
1790	chr14	64749029	64750351	−	ESR2	0x1
1791	chr14	65590559	65591762	−	MAX	0x0
1792	chr14	68265192	68266392	+	RAD51B	0x2
1793	chr14	69259066	69260239	−	ZFP36L1	0x2
1794	chr14	70235277	70236409	+	SR5F5	0x0
1795	chr14	70827039	70828233	+	ADAM21	0x0
1796	chr14	71050827	71051971	−	MEDS	0x0
1797	chr14	73395835	73397193	−	DPF3	0x0
1798	chr14	73637050	73638259	+	PSEN1	0x0
1799	chr14	73658933	73660059	+	PSEN1	0x0
1800	chr14	73750395	73751600	−	NUMB	0x0
1801	chr14	75068529	75069738	−	LTBP2	0x2
1802	chr14	75358451	75359654	+	DLST	0x0
1803	chr14	75496694	75497909	−	MLH3	0x0
1804	chr14	75575913	75577091	−	NEK9	0x2
1805	chr14	75600401	75601539	−	TMED10	0x0
1806	chr14	76528971	76530189	+	IFT43	0x0
1807	chr14	76637656	76638879	+	C14orf118	0x0
1808	chr14	76663629	76664745	+	C14orf118	0x0
1809	chr14	77256334	77257559	−	ANGEL1	0x0
1810	chr14	78173934	78175091	+	SLIRP	0x0
1811	chr14	81668501	81669733	−	SNORA79	0x0
1812	chr14	85737717	85738922	+	FLRT2	0x0
1813	chr14	89043389	89044605	+	ZC3H14	0x0
1814	chr14	89078709	89079907	+	ZC3H14	0x0
1815	chr14	89299285	89300522	+	TTC8	0x0
1816	chr14	90051483	90052669	+	PRO1768	0x0
1817	chr14	90178358	90179578	+	PRO1768	0x0
1818	chr14	90564181	90565327	−	EFCAB11	0x0
1819	chr14	91816631	91817828	−	CCDC88C	0x0
1820	chr14	93406578	93408201	−	ITPK1	0x0
1821	chr14	95192789	95194001	+	SERPINA13	0x0
1822	chr14	95999181	96000528	−	SCARNA13	0x0
1823	chr14	95999181	96000528	−	SNHG10	0x0
1824	chr14	96428328	96429515	−	TCL1A	0x0
1825	chr14	96788184	96789377	−	ATG2B	0x0
1826	chr14	96850446	96851673	+	C14orf129	0x0
1827	chr14	97003083	97004318	+	PAPOLA	0x0
1828	chr14	97299331	97300523	+	VRK1	0x0
1829	chr14	97303953	97305166	+	VRK1	0x0
1830	chr14	97588455	97589675	+	VRK1	0x0
1831	chr14	99438779	99440087	−	BCL11B	0x2
1832	chr14	99871011	99872156	−	SETD3	0x0
1833	chr14	99927008	99928201	−	SETD3	0x0
1834	chr14	99978119	99979271	−	CCDC85C	0x0
1835	chr14	99980306	99981513	−	CCDC85C	0x0
1836	chr14	100704883	100706065	+	YY1	0x0
1837	chr14	102451533	102452778	+	DYNC1H1	0x0
1838	chr14	102485774	102486912	+	DYNC1H1	0x0
1839	chr14	102513570	102514767	+	DYNC1H1	0x0
1840	chr14	102515579	102516643	+	DYNC1H1	0x0
1841	chr14	102547003	102548556	−	HSP90AA1	0x2
1842	chr14	102551792	102552968	−	HSP90AA1	0x2
1843	chr14	102792163	102793304	+	ZNF839	0x0
1844	chr14	102797439	102798576	+	ZNF839	0x0
1845	chr14	102972147	102973298	−	ANKRD9	0x0
1846	chr14	103284894	103286072	+	TRAF3	0x2
1847	chr14	103375057	103376164	+	TRAF3	0x2
1848	chr14	103601516	103602707	+	TNFAIP2	0x0
1849	chr14	103803650	103804881	+	EIF5	0x0
1850	chr14	103803650	103804881	+	SNORA28	0x0
1851	chr14	103985494	103987405	−	CKB	0x0
1852	chr14	104131617	104132836	−	KLC1	0x0
1853	chr14	104378332	104379524	−	C14orf2	0x0
1854	chr14	104479474	104480652	+	TDRD9	0x0
1855	chr14	105235359	105236649	−	AKT1	0x2
1856	chr14	105715971	105717135	−	BRF1	0x1
1857	chr14	105716708	105717810	+	BTBD6	0x0
1858	chr14	105752951	105754079	−	BRF1	0x1
1859	chr14	105849686	105850785	+	PACS2	0x0
1860	chr14	105926114	105927310	+	MTA1	0x2
1861	chr14	105934900	105936046	+	MTA1	0x2
1862	chr15	21936754	21937923	−	LOC646214	0x0
1863	chr15	24925724	24926901	+	C15orf2	0x2
1864	chr15	25683452	25684651	−	UBE3A	0x4
1865	chr15	25781530	25782728	+	SNORD109A	0x4
1866	chr15	25781530	25782728	+	SNORD109B	0x4
1867	chr15	28491389	28492502	−	HERC2	0x2
1868	chr15	28505439	28506582	−	HERC2	0x2
1869	chr15	29335946	29337183	+	APBA2	0x0
1870	chr15	29345646	29346846	+	APBA2	0x0
1871	chr15	31745052	31746201	−	OTUD7A	0x0
1872	chr15	34251063	34252240	−	AVEN	0x0
1873	chr15	34633527	34634962	−	NOP10	0x0
1874	chr15	34781617	34782779	−	GOLGA8B	0x0
1875	chr15	37014652	37015883	+	C15orf41	0x0
1876	chr15	37255197	37256324	−	MEIS2	0x0
1877	chr15	40833292	40834457	−	MRPL42P5	0x0
1878	chr15	41036799	41038022	−	FAM82A2	0x0
1879	chr15	41270810	41271987	−	INO80	0x0
1880	chr15	41315423	41316571	−	INO80	0x0
1881	chr15	41683649	41684911	−	NDUFAF1	0x0
1882	chr15	41987838	41989218	+	MGA	0x2
1883	chr15	42002771	42004041	+	MGA	0x2
1884	chr15	42620396	42621594	−	GANC	0x0
1885	chr15	42706180	42707487	−	ZFP106	0x0
1886	chr15	42962748	42963944	+	STARD9	0x0
1887	chr15	43283722	43284928	−	UBR1	0x2
1888	chr15	44038200	44039385	+	PDIA3	0x0
1889	chr15	44093201	44094397	+	C15orf63	0x0
1890	chr15	44093201	44094397	+	SERF2-C15ORF63	0x0
1891	chr15	44243568	44244787	−	FRMD5	0x0
1892	chr15	44707143	44708328	+	CASC4	0x0
1893	chr15	44853224	44854435	+	EIF3J	0x0
1894	chr15	44855288	44856463	+	EIF3J	0x0
1895	chr15	45039370	45040570	+	TRIM69	0x0
1896	chr15	45490204	45491403	−	SHF	0x0
1897	chr15	45492010	45493176	−	SHF	0x0
1898	chr15	45492781	45493978	+	DUOX1	0x0
1899	chr15	47619874	47621023	+	SEMA6D	0x0
1900	chr15	47699587	47700788	+	SEMA6D	0x0
1901	chr15	48729413	48730591	−	FBN1	0x0
1902	chr15	49170975	49172607	+	EID1	0x2
1903	chr15	51223596	51224840	+	AP4E1	0x0
1904	chr15	52841907	52843027	−	ARPP13	0x0
1905	chr15	55874281	55875380	−	PYGO1	0x0
1906	chr15	59040732	59041932	−	ADAM10	0x2
1907	chr15	59431774	59432875	+	CCNB2	0x0
1908	chr15	59968844	59970052	−	BNIP2	0x0
1909	chr15	60576764	60577938	+	FOXB1	0x0
1910	chr15	61501060	61510500	+	RORA	0x0
1911	chr15	64791589	64792900	+	ZNF609	0x0
1912	chr15	64856192	64857385	+	ZNF609	0x0
1913	chr15	65587813	65589092	+	KBTBD13	0x0
1914	chr15	65596449	65597712	+	KBTBD13	0x0
1915	chr15	66433059	66434274	−	MEGF11	0x0
1916	chr15	66496826	66498012	−	MEGF11	0x0
1917	chr15	66637503	66638647	−	SCARNA14	0x0
1918	chr15	66639053	66640252	−	SCARNA14	0x0
1919	chr15	66792791	66794211	−	RPL4	0x0
1920	chr15	66792791	66794211	−	SNORD18C	0x0
1921	chr15	66794418	66796231	−	RPL4	0x0
1922	chr15	66794418	66796231	−	SNORD16	0x0
1923	chr15	66794418	66796231	−	SNORD18A	0x0
1924	chr15	66794418	66796231	−	SNORD18B	0x0
1925	chr15	67511428	67512557	−	AAGAB	0x0
1926	chr15	68496759	68497953	−	CALML4	0x0
1927	chr15	68499340	68500439	−	CLN6	0x0
1928	chr15	68572922	68574070	+	FEM1B	0x0
1929	chr15	69070758	69072796	−	ANP32A	0x1
1930	chr15	69079609	69080756	−	ANP32A	0x1
1931	chr15	69100468	69101612	−	ANP32A-IT1	0x0
1932	chr15	69494074	69495240	+	MIR548H4	0x0
1933	chr15	69738521	69739744	+	KIF23	0x0
1934	chr15	69747224	69748423	+	RPLP1	0x0
1935	chr15	70389486	70390685	−	TLE3	0x0
1936	chr15	70481875	70483051	+	C15orf50	0x0
1937	chr15	71456865	71458080	−	CT62	0x0
1938	chr15	72337357	72338555	+	SENP8	0x0
1939	chr15	72486311	72487490	−	GRAMD2	0x0
1940	chr15	72490926	72492479	−	PKM2	0x0
1941	chr15	72546097	72547249	−	PARP6	0x0
1942	chr15	72766136	72767238	+	ARIH1	0x0
1943	chr15	73043229	73044383	−	ADPGK	0x0
1944	chr15	73408453	73409650	+	NEO1	0x1
1945	chr15	74851876	74853097	+	ARID3B	0x1
1946	chr15	75132127	75133316	−	ULK3	0x0
1947	chr15	75628401	75629629	+	COMMD4	0x0
1948	chr15	76584313	76585531	−	ETFA	0x0
1949	chr15	77224273	77225393	+	RCN2	0x1
1950	chr15	77337848	77339156	−	TSPAN3	0x0
1951	chr15	77362838	77363961	−	TSPAN3	0x0
1952	chr15	77969913	77971109	−	LINGO1	0x0
1953	chr15	78833666	78834832	+	PSMA4	0x0
1954	chr15	78881867	78883066	+	CHRNA5	0x0
1955	chr15	78884931	78886120	+	CHRNA5	0x0
1956	chr15	79152336	79153574	+	MORF4L1	0x0
1957	chr15	80993689	80994882	+	FAM108C1	0x0
1958	chr15	81270066	81271359	−	MESDC2	0x0
1959	chr15	81557467	81558641	−	STARD5	0x0
1960	chr15	82466075	82467253	−	EFTUD1	0x0
1961	chr15	83684818	83686067	−	BTBD1	0x0
1962	chr15	83857545	83858740	−	HDGFRP3	0x0
1963	chr15	84515575	84516733	−	LOC388152	0x0
1964	chr15	84819674	84820905	+	LOC100505679	0x0
1965	chr15	85234210	85235385	−	SEC11A	0x0
1966	chr15	85337100	85338312	+	ZNF592	0x0
1967	chr15	85628321	85629513	+	PDE8A	0x0
1968	chr15	86111157	86112347	+	AKAP13	0x2
1969	chr15	86260146	86261296	+	AKAP13	0x2
1970	chr15	88654304	88655504	+	LOC283738	0x0
1971	chr15	89743411	89744512	+	ABHD2	0x0
1972	chr15	89825525	89826904	+	FANCI	0x0
1973	chr15	89859503	89860736	+	FANCI	0x0
1974	chr15	89877748	89878974	+	FANCI	0x0
1975	chr15	90146668	90147889	+	C15orf42	0x0
1976	chr15	90610429	90611599	+	ZNF710	0x0
1977	chr15	90814312	90815850	+	NGRN	0x0
1978	chr15	90907212	90908788	+	ZNF774	0x0
1979	chr15	91185812	91187013	+	CRTC3	0x2
1980	chr15	91425207	91426364	+	FURIN	0x0
1981	chr15	91432876	91434053	−	HDDC3	0x0
1982	chr15	91478248	91479432	+	UNC45A	0x0
1983	chr15	91516850	91517974	−	PRC1	0x2
1984	chr15	93255471	93256642	+	ASB9P1	0x0
1985	chr15	93586832	93588055	−	RGMA	0x0
1986	chr15	96288506	96289758	+	LOC145820	0x0
1987	chr15	100648661	100649816	−	ADAMTS17	0x0
1988	chr15	100765299	100766413	−	ADAMTS17	0x0
1989	chr15	100870564	100871790	−	ADAMTS17	0x0
1990	chr15	101480773	101482171	+	LRRK1	0x2
1991	chr15	101825007	101826228	−	SNRPA1	0x0
1992	chr15	102181636	102182846	−	TM2D3	0x0
1993	chr16	143816	144957	+	MPG	0x0
1994	chr16	235472	236640	−	LUC7L	0x0
1995	chr16	342848	344050	−	AXIN1	0x1
1996	chr16	396145	397340	−	AXIN1	0x1
1997	chr16	448859	451026	+	NME4	0x0
1998	chr16	589506	590634	+	MIR3176	0x0
1999	chr16	595185	596399	+	SOLH	0x0
2000	chr16	601507	602707	+	SOLH	0x0
2001	chr16	683792	685117	−	C16orf13	0x0
2002	chr16	723557	724706	+	RHOT2	0x0
2003	chr16	733573	734707	−	JMJD8	0x0
2004	chr16	733573	734707	−	WDR24	0x0
2005	chr16	783112	784246	−	NARFL	0x0
2006	chr16	787182	788296	−	NARFL	0x0
2007	chr16	841316	842543	+	CHTF18	0x0
2008	chr16	941830	943035	−	LMF1	0x0
2009	chr16	1419680	1420859	−	UNKL	0x0
2010	chr16	1509920	1511053	−	CLCN7	0x0
2011	chr16	1793752	1795078	+	MAPK8IP3	0x2
2012	chr16	2011358	2012506	+	NDUFB10	0x0
2013	chr16	2012334	2013692	−	RPS2	0x0
2014	chr16	2012334	2013692	−	SNORA10	0x0
2015	chr16	2012334	2013692	−	SNORA64	0x0
2016	chr16	2127155	2128344	+	TSC2	0x1
2017	chr16	2129738	2130819	+	TSC2	0x1
2018	chr16	2204448	2205682	−	SNORD60	0x0
2019	chr16	2262814	2263925	−	PGP	0x0
2020	chr16	2302820	2304024	−	RNPS1	0x0
2021	chr16	2325778	2326930	−	ABCA3	0x0
2022	chr16	2507661	2508867	+	CCNF	0x0
2023	chr16	2551481	2552720	+	TBC1D24	0x0
2024	chr16	2669190	2670380	−	ERVK13-1	0x0
202S	chr16	2816749	2818757	+	SRRM2	0x0
2026	chr16	3103594	3104769	−	CCDC64B	0x0
2027	chr16	3135604	3136834	+	IL32	0x0
2028	chr16	3183893	3185039	−	MGC3771	0x0
2029	chr16	3206822	3207998	−	MGC3771	0x0
2030	chr16	3707612	3708771	−	TRAP1	0x0
2031	chr16	3738655	3739754	−	TRAP1	0x0
2032	chr16	3776638	3777807	−	CREBBP	0x1
2033	chr16	3853492	3854682	−	CREBBP	0x1
2034	chr16	3899742	3901495	−	CREBBP	0x1
2035	chr16	4312072	4313247	−	TFAP4	0x0
2036	chr16	4585148	4586317	−	C16orf5	0x0
2037	chr16	4631453	4632577	−	FAM100A	0x0
2038	chr16	4780498	4781691	−	ANKS3	0x0
2039	chr16	4809968	4811154	−	ZNF500	0x0
2040	chr16	4930725	4931953	+	UBN1	0x0
2041	chr16	9202390	9203489	+	C16orf72	0x0
2042	chr16	9732686	9733886	+	MIR548X	0x0
2043	chr16	10623788	10625100	−	EMP2	0x0
2044	chr16	11118150	11119355	+	CLEC16A	0x0
2045	chr16	11795285	11796473	−	TXNDC11	0x0
2046	chr16	11982629	11983709	−	GSPT1	0x0
2047	chr16	11989914	11991031	−	GSPT1	0x0
2048	chr16	14247481	14248682	+	MKL2	0x0
2049	chr16	15154201	15155400	−	RRN3	0x0
2050	chr16	15224518	15225828	−	MIR3180-4	0x0
2051	chr16	15959530	15960686	−	FOPNL	0x0
2052	chr16	16103077	16104257	+	ABCC1	0x0
2053	chr16	16180120	16181312	+	ABCC1	0x0
2054	chr16	16231673	16232855	+	ABCC1	0x0
2055	chr16	18367186	18368355	+	ABCC6P1	0x0
2056	chr16	18795494	18796703	−	RPS15A	0x0
2057	chr16	21964106	21965352	−	UQCRC2	0x2
2058	chr16	22206429	22207666	−	CDR2	0x0
2059	chr16	22236504	22237625	−	EEF2K	0x0
2060	chr16	23154325	23155505	−	USP31	0x0
2061	chr16	23443115	23444292	+	SCNN1B	0x0
2062	chr16	23455520	23456673	−	COG7	0x0
2063	chr16	23518784	23519913	−	GGA2	0x0
2064	chr16	26772167	26773347	−	NSMCE1	0x0
2065	chr16	28109306	28110513	−	XPO6	0x0
2066	chr16	28165013	28166113	−	XPO6	0x0
2067	chr16	28172868	28174090	+	SBK1	0x0
2068	chr16	28178211	28179388	−	XPO6	0x0
2069	chr16	28222170	28223312	−	XPO6	0x0
2070	chr16	28488127	28489342	−	CLN3	0x0
2071	chr16	28502619	28503773	−	CLN3	0x0
2072	chr16	28735596	28736768	+	EIF3C	0x0
2073	chr16	28735596	28736768	+	EIF3CL	0x0
2074	chr16	29620126	29621279	−	SLC7A5P1	0x0
2075	chr16	29818410	29819625	+	MAZ	0x0
2076	chr16	29821157	29822740	+	MAZ	0x0
2077	chr16	29830643	29831878	+	C16orf53	0x0
2078	chr16	29830643	29831878	+	MVP	0x0
2079	chr16	30076596	30077792	+	ALDOA	0x0
2080	chr16	30078033	30079171	+	ALDOA	0x0
2081	chr16	30079608	30080725	+	ALDOA	0x0
2082	chr16	30345960	30347162	−	LOC595101	0x0
2083	chr16	30367895	30369061	−	TBC1D10B	0x0
2084	chr16	30369950	30371830	−	TBC1D10B	0x0
2085	chr16	30482481	30483615	+	ITGAL	0x0
2086	chr16	30662533	30663730	+	PRR14	0x0
2087	chr16	30680929	30682096	+	FBRS	0x0
2088	chr16	30721321	30722534	+	SNORA30	0x0
2089	chr16	30721321	30722534	+	SRCAP	0x0
2090	chr16	30734492	30735698	+	SRCAP	0x0
2091	chr16	30749886	30751115	+	SRCAP	0x0
2092	chr16	30762261	30763449	+	PHKG2	0x0
2093	chr16	30785855	30786949	+	RNF40	0x0
2094	chr16	30898461	30899560	−	BCL7C	0x0
2095	chr16	30995147	30996395	+	SETD1A	0x0
2096	chr16	31055455	31056660	+	STX4	0x0
2097	chr16	31101627	31103190	−	VKORC1	0x0
2098	chr16	33959014	33960199	−	LINC00273	0x0
2099	chr16	33963060	33964589	+	LOC283914	0x0
2100	chr16	46946475	46947651	+	GPT2	0x0
2101	chr16	46949560	46950994	+	GPT2	0x0
2102	chr16	47161753	47162900	−	NETO2	0x0
2103	chr16	47176155	47177315	−	NETO2	0x0
2104	chr16	47502596	47503917	+	PHKB	0x0
2105	chr16	47530809	47531908	+	PHKB	0x0
2106	chr16	48277848	48278972	+	LONP2	0x0
2107	chr16	48387030	48388180	+	LONP2	0x0
2108	chr16	49557027	49558211	−	ZNF423	0x0
2109	chr16	49604532	49605679	−	ZNF423	0x0
2110	chr16	50138880	50140042	+	HEATR3	0x0
2111	chr16	53468212	53469426	+	RBL2	0x1
2112	chr16	54018126	54019355	+	FTO	0x0
2113	chr16	57333351	57334551	+	ARL2BP	0x0
2114	chr16	57333796	57335000	−	PLLP	0x0
2115	chr16	57770451	57771687	+	KATNB1	0x0
2116	chr16	58194850	58196051	−	CSNK2A2	0x0
2117	chr16	58506204	58507370	+	NDRG4	0x1
2118	chr16	58581850	58583095	−	SNORA46	0x0
2119	chr16	58593207	58594416	−	CNOT1	0x2
2120	chr16	58593207	58594416	−	SNORA50	0x0
2121	chr16	58636236	58637361	−	CNOT1	0x2
2122	chr16	59573507	59574718	+	SETD6	0x0
2123	chr16	61776537	61777739	−	CDH8	0x0
2124	chr16	66583830	66585064	+	CKLF	0x0
2125	chr16	66583830	66585064	+	CKLF-CMTM1	0x0
2126	chr16	66651623	66652756	−	CMTM4	0x0
2127	chr16	66857453	66858552	−	NAE1	0x0
2128	chr16	67355018	67356243	−	KCTD19	0x0
2129	chr16	67644395	67645577	−	ACD	0x4
2130	chr16	67644742	67646514	+	CTCF	0x1
2131	chr16	67670055	67671257	+	CTCF	0x1
2132	chr16	68155794	68157476	+	NFATC3	0x0
2133	chr16	68537173	68538388	+	ZFP90	0x0
2134	chr16	69362090	69363244	−	COG8	0x0
2135	chr16	69362090	69363244	−	PDF	0x0
2136	chr16	69375976	69377216	+	NIP7	0x0
2137	chr16	69641676	69642775	+	NFAT5	0x0
2138	chr16	70282376	70283535	−	EXOSC6	0x0
2139	chr16	70380666	70382034	+	DDX19A	0x0
2140	chr16	70412278	70413437	−	ST3GAL2	0x0
2141	chr16	70567748	70568934	+	SF3B3	0x0
2142	chr16	70598735	70599882	+	SF3B3	0x0
2143	chr16	70600812	70601947	+	SF3B3	0x0
2144	chr16	70724351	70725450	−	VAC14	0x0
2145	chr16	72238271	72239450	−	PMFBP1	0x0
2146	chr16	72984070	72985255	−	ZFHX3	0x1
2147	chr16	72990914	72992079	−	ZFHX3	0x1
2148	chr16	72992940	72994069	−	ZFHX3	0x1
2149	chr16	73047809	73049165	−	ZFHX3	0x1
2150	chr16	74714271	74715389	−	MLKL	0x0
2151	chr16	75289855	75291011	−	BCAR1	0x0
2152	chr16	79630494	79631584	−	MAF	0x1
2153	chr16	81030333	81031467	−	CMC2	0x0
2154	chr16	81744479	81745663	+	CMIP	0x0
2155	chr16	81995033	81996350	+	PLCG2	0x2
2156	chr16	82195015	82196190	−	MPHOSPH6	0x0
2157	chr16	84216501	84217600	−	TAF1C	0x0
2158	chr16	84734892	84736093	+	USP10	0x0
2159	chr16	84778008	84779365	+	USP10	0x0
2160	chr16	85244625	85245831	+	LOC400548	0x0
2161	chr16	85394186	85395412	+	LINC00311	0x0
2162	chr16	85443986	85445195	+	LINC00311	0x0
2163	chr16	85660061	85661260	+	KIAA0182	0x0
2164	chr16	85808485	85809616	−	COX4NB	0x0
2165	chr16	87364296	87365490	−	FBXO31	0x1
2166	chr16	87398201	87399306	−	FBXO31	0x1
2167	chr16	87469465	87470642	−	ZCCHC14	0x0
2168	chr16	87737922	87739118	−	KLHDC4	0x0
2169	chr16	88060540	88061765	+	BANP	0x1
2170	chr16	88083221	88084320	+	BANP	0x1
2171	chr16	88817646	88818825	−	PIEZO1	0x0
2172	chr16	88872808	88873963	+	CDT1	0x0
2173	chr16	89164503	89165709	+	ACSF3	0x0
2174	chr16	89371092	89372297	−	ANKRD11	0x0
2175	chr16	89497144	89498290	−	ANKRD11	0x0
2176	chr16	89543379	89550500	−	ANKRD11	0x0
2177	chr16	89595342	89596458	+	SPG7	0x0
2178	chr16	89627259	89628503	+	RPL13	0x0
2179	chr16	89627259	89628503	+	SNORD68	0x0
2180	chr16	89629746	89630946	+	RPL13	0x0
2181	chr16	89720957	89722136	+	C16orf55	0x0
2182	chr16	89759982	89761224	+	CDK10	0x0
2183	chr16	89762227	89763431	−	SPATA2L	0x0
2184	chr16	89783657	89784775	+	LOC100128881	0x0
2185	chr16	89803908	89805002	+	ZNF276	0x0
2186	chr16	89804541	89805669	−	FANCA	0x2
2187	chr16	89830638	89831758	−	FANCA	0x2
2188	chr16	89835725	89837364	−	FANCA	0x2
2189	chr16	89851003	89852132	−	FANCA	0x2
2190	chr16	89960891	89962086	+	TCF25	0x0
2191	chr16	89966465	89967671	+	TCF25	0x0
2192	chr16	89975246	89976652	−	TCF25	0x0
2193	chr16	90019017	90020436	+	DEF8	0x0
2194	chr16	90027401	90028606	+	DEF8	0x0
2195	chr16	90071461	90072626	−	DBNDD1	0x0
2196	chr16	90094687	90095934	+	GAS8	0x0
2197	chr17	420039	421215	−	VPS53	0x1
2198	chr17	421588	422752	−	VPS53	0x1
2199	chr17	809734	810881	−	NXN	0x0
2200	chr17	877224	878419	+	TIMM22	0x0
2201	chr17	906054	907251	+	TIMM22	0x0
2202	chr17	907914	909091	−	ABR	0x0
2203	chr17	975303	976505	−	ABR	0x0
2204	chr17	1247548	1249295	−	YWHAE	0x2
2205	chr17	1302901	1304079	−	YWHAE	0x2
2206	chr17	1367797	1369135	−	MYO1C	0x0
2207	chr17	1870297	1871457	−	RTN4RL1	0x0
2208	chr17	2091648	2092874	+	SRR	0x0
2209	chr17	2202637	2203736	−	SMG6	0x0
2210	chr17	2231890	2233069	−	SNORD91B	0x0
2211	chr17	2231890	2233069	−	TSR1	0x0
2212	chr17	2289272	2290479	−	MNT	0x0
2213	chr17	2758169	2759392	+	RAP1GAP2	0x0
2214	chr17	3727428	3728604	−	C17orf85	0x0
2215	chr17	3774868	3776203	−	CAMKK1	0x0
2216	chr17	3989255	3990394	−	ZZEF1	0x2
2217	chr17	4848985	4850149	−	PFN1	0x1
2218	chr17	4927219	4928332	+	KIF1C	0x2
2219	chr17	5011951	5013308	−	ZNF232	0x0
2220	chr17	5192114	5193285	+	RABEP1	0x2
2221	chr17	5347087	5348274	−	DHX33	0x0
2222	chr17	7128624	7130033	−	DVL2	0x0
2223	chr17	7143329	7144561	−	GABARAP	0x1
2224	chr17	7214768	7215867	+	EIF5A	0x2
2225	chr17	7310728	7311838	+	NLGN2	0x0
2226	chr17	7477573	7478698	+	EIF4A1	0x0
2227	chr17	7477573	7478598	+	SENP3-EIF4A1	0x0
2228	chr17	7477573	7478698	+	SNORA48	0x0
2229	chr17	7479570	7481901	+	EIF4A1	0x0
2230	chr17	7479570	7481901	+	SENP3-EIF4A1	0x0
2231	chr17	7479570	7481901	+	SNORA67	0x0
2232	chr17	7479570	7481901	+	SNORD10	0x0
2233	chr17	7571798	7572976	−	TP53	0x1
2234	chr17	7759946	7761139	−	LSMD1	0x0
2235	chr17	7809090	7810209	+	CHD3	0x2
2236	chr17	7809090	7810209	+	SCARNA21	0x0
2237	chr17	7848570	7849762	+	CNTROB	0x0
2238	chr17	8023063	8024273	−	HES7	0x0
2239	chr17	8023683	8024894	+	MIR4314	0x0
2240	chr17	8076195	8077469	−	TMEM107	0x0
2241	chr17	8089692	8090869	+	MIR3676	0x0
2242	chr17	8089692	8090869	+	MIR4521	0x0
2243	chr17	8377996	8379137	−	MYH10	0x0
2244	chr17	14608210	14609470	−	CDRT15	0x0
2245	chr17	15918092	15919219	+	TTC19	0x0
2246	chr17	16132196	16133391	+	PIGL	0x0
2247	chr17	16343991	16345208	+	C17orf76-AS1	0x0
2248	chr17	16343991	16345208	+	SNORD65	0x0
2249	chr17	17089072	17090238	+	MPRIP	0x0
2250	chr17	17286493	17287902	−	C0PS3	0x2
2251	chr17	17634942	17636091	+	RAI1	0x0
2252	chr17	17999746	18000896	+	DRG2	0x0
2253	chr17	18111909	18113101	+	ALKBH5	0x0
2254	chr17	18177405	18178544	−	TOP3A	0x0
2255	chr17	18562696	18563882	+	ZNF286B	0x0
2256	chr17	18964696	18965964	+	SLC5A10	0x0
2257	chr17	19015303	19016503	−	GRAP	0x0
2258	chr17	19090777	19092061	+	GRAPL	0x0
2259	chr17	19092840	19094050	−	GRAP	0x0
2260	chr17	19349188	19350394	−	MFAP4	0x0
2261	chr17	19355037	19356234	+	RNF112	0x0
2262	chr17	19568464	19569565	+	ALDH3A2	0x0
2263	chr17	20903023	20904171	−	USP22	0x0
2264	chr17	26368250	26369432	+	NLK	0x0
2265	chr17	26794566	26795779	+	SLC13A2	0x0
2266	chr17	26918992	26920362	−	SPAG5	0x0
2267	chr17	26959602	26960700	−	KIAA0100	0x0
2268	chr17	27047016	27048207	+	RPL23A	0x0
2269	chr17	27047016	27048207	+	SNORD42B	0x0
2270	chr17	27049068	27051266	+	RPL23A	0x0
2271	chr17	27049068	27051266	+	SNORD42A	0x0
2272	chr17	27049068	27051266	+	SNORD4A	0x0
2273	chr17	27049068	27051266	+	SNORD4B	0x0
2274	chr17	27076052	27077263	+	TRAF4	0x0
2275	chr17	27134427	27135693	−	C17orf63	0x0
2276	chr17	27206815	27207989	−	FLOT2	0x0
2277	chr17	27250434	27251617	−	PHF12	0x0
2278	chr17	27330860	27332058	−	SEZ6	0x0
2279	chr17	27586017	27587151	−	NUFIP2	0x0
2280	chr17	27589485	27590890	−	NUFIP2	0x0
2281	chr17	27597552	27598763	−	NUFIP2	0x0
2282	chr17	27613073	27614247	−	NUFIP2	0x0
2283	chr17	27620125	27621304	−	NUFIP2	0x0
2284	chr17	27876749	27877967	+	TAOK1	0x0
2285	chr17	28793244	28794488	+	CPD	0x2
2286	chr17	29151064	29152280	−	CRLF3	0x0
2287	chr17	29876577	29877796	+	MIR193A	0x0
2288	chr17	30178363	30179685	−	C17orf79	0x0
2289	chr17	30322093	30323192	+	SUZ12	0x2
2290	chr17	30323258	30324460	+	SUZ12	0x2
2291	chr17	30327053	30328256	+	SUZ12	0x2
2292	chr17	30701748	30703107	+	ZNF207	0x0
2293	chr17	30729721	30730945	+	ZNF207	0x0
2294	chr17	31149233	31150434	+	TMEM98	0x0
2295	chr17	33338521	33339709	−	RAD51L3-RFFL	0x0
2296	chr17	33338521	33339709	−	RFFL	0x0
2297	chr17	33477601	33478846	−	NLE1	0x0
2298	chr17	34005816	34007062	+	AP281	0x0
2299	chr17	34051812	34052960	+	AP281	0x0
2300	chr17	34216112	34217346	+	TAF15	0x0
2301	chr17	34867890	34869254	−	MYO19	0x0
2302	chr17	35463729	35464880	−	ACACA	0x0
2303	chr17	35609261	35610459	−	ACACA	0x0
2304	chr17	36907500	36908659	−	PCGF2	0x1
2305	chr17	36923201	36924315	−	PIP4K2B	0x0
2306	chr17	36933509	36934767	−	PIP4K2B	0x0
2307	chr17	37008384	37009879	−	RPL23	0x0
2308	chr17	37008384	37009879	−	SNORA21	0x0
2309	chr17	37310065	37311369	−	ARL5C	0x0
2310	chr17	37360307	37361530	+	RPL19	0x0
2311	chr17	38187243	38188407	−	MED24	0x0
2312	chr17	38292372	38293524	+	MSL1	0x0
2313	chr17	38544516	38546023	−	TOP2A	0x0
2314	chr17	38546963	38548087	−	TOP2A	0x0
2315	chr17	38555669	38556813	−	TOP2A	0x0
2316	chr17	39623661	39624919	+	LOC100505782	0x0
2317	chr17	39682054	39683217	−	KRT19	0x0
2318	chr17	39919253	39920390	−	JUP	0x1
2319	chr17	39976137	39977291	+	FKBP10	0x0
2320	chr17	40022691	40023931	−	ACLY	0x0
2321	chr17	40041357	40042582	−	ACLY	0x0
2322	chr17	40051029	40052128	−	ACLY	0x0
2323	chr17	40066060	40067304	−	ACLY	0x0
2324	chr17	40150541	40151724	−	DNAJC7	0x0
2325	chr17	40276463	40277602	−	RAB5C	0x0
2326	chr17	40997873	40999063	+	AOC2	0x0
2327	chr17	41166535	41167621	−	VAT1	0x0
2328	chr17	41464126	41465330	−	LOC100130581	0x0
2329	chr17	41477626	41478857	+	ARL4D	0x0
2330	chr17	41893195	41894405	−	MPP3	0x1
2331	chr17	42124839	42126012	−	LSM12	0x0
2332	chr17	42143070	42144243	−	LSM12	0x0
2333	chr17	42269530	42270800	−	ATXN7L3	0x0
2334	chr17	42283758	42284942	−	UBTF	0x0
2335	chr17	42291123	42292222	−	UBTF	0x0
2336	chr17	42429663	42430895	−	GRN	0x0
2337	chr17	42472130	42475225	−	GPATCH8	0x0
2338	chr17	42563669	42564836	−	GPATCH8	0x0
2339	chr17	42858464	42859563	−	ADAM11	0x0
2340	chr17	42927693	42928792	−	EFTUD2	0x0
2341	chr17	43011561	43012778	−	KIF18B	0x0
2342	chr17	43112655	43113866	−	DCAKD	0x0
2343	chr17	43127402	43129550	−	DCAKD	0x0
2344	chr17	43158651	43159849	+	NMT1	0x0
2345	chr17	43188503	43189680	−	PLCD3	0x0
2346	chr17	43552039	43553599	−	MIR4315-1	0x0
2347	chr17	43552039	43553599	−	MIR4315-2	0x0
2348	chr17	43552039	43553599	−	PLEKHM1	0x0
2349	chr17	44107289	44109182	−	KANSL1	0x0
2350	chr17	44121458	44122619	−	KANSL1	0x0
2351	chr17	44143350	44144558	−	KANSL1	0x0
2352	chr17	44235813	44236965	−	KANSL1	0x0
2353	chr17	44248825	44250127	−	KANSL1	0x0
2354	chr17	44892011	44893187	+	WNT9B	0x0
2355	chr17	45700639	45701871	+	NPEPPS	0x0
2356	chr17	45740976	45743040	+	KPNB1	0x0
2357	chr17	45749870	45751463	+	KPNB1	0x0
2358	chr17	45759557	45760750	+	KPNB1	0x0
2359	chr17	46048089	46049200	+	CDK5RAP3	0x0
2360	chr17	46146996	46148371	−	CBX1	0x0
2361	chr17	46555948	46557104	+	HOXB-AS3	0x0
2362	chr17	46672630	46673780	−	HOXB6	0x0
2363	chr17	46674823	46676013	−	HOXB6	0x0
2364	chr17	46689629	46690750	−	HOXB8	0x0
2365	chr17	46698671	46699886	−	HOXB9	0x0
2366	chr17	47026177	47027373	−	SNF8	0x0
2367	chr17	47102139	47103238	+	IGF2BP1	0x0
2368	chr17	47103331	47104443	+	IGF2BP1	0x0
2369	chr17	47128290	47131034	+	IGF2BP1	0x0
2370	chr17	47269322	47270552	+	ABI3	0x2
2371	chr17	47370381	47371514	−	ZNF652	0x0
2372	chr17	47438823	47439984	−	ZNF652	0x0
2373	chr17	47698699	47699875	−	SPOP	0x2
2374	chr17	48211639	48212824	−	PPP1R9B	0x0
2375	chr17	48458394	48459935	−	LRRC59	0x0
2376	chr17	49238557	49239765	+	NME1	0x1
2377	chr17	49238557	49239765	+	NME1-NME2	0x0
2378	chr17	49243309	49244511	+	NME1-NME2	0x0
2379	chr17	49243309	49244511	+	NME2	0x0
2380	chr17	50173256	50174452	+	UTP18	0x0
2381	chr17	54908462	54909643	−	C17orf67	0x0
2382	chr17	54965631	54966927	−	TRIM25	0x0
2383	chr17	55536824	55538020	+	MSI2	0x0
2384	chr17	55756729	55757945	+	MSI2	0x0
2385	chr17	55760969	55762149	+	MSI2	0x0
2386	chr17	55866332	55867485	+	MSI2	0x0
2387	chr17	56078023	56079230	−	SRSF1	0x2
2388	chr17	56081814	56083329	−	SRSF1	0x2
2389	chr17	56083848	56084941	−	SRSF1	0x2
2390	chr17	56566533	56567635	−	MTMR4	0x0
2391	chr17	56902493	56903592	+	PPM1E	0x2
2392	chr17	57188247	57189567	−	SKA2	0x0
2393	chr17	57317303	57318598	+	GDPD1	0x0
2394	chr17	57474126	57475693	+	YPEL2	0x0
2395	chr17	57684974	57686173	+	DHX40	0x0
2396	chr17	57771333	57772704	+	CLTC	0x2
2397	chr17	57808269	57809459	+	VMP1	0x0
2398	chr17	57957769	57958998	−	TUBD1	0x0
2399	chr17	58010067	58011229	+	RPS6KB1	0x2
2400	chr17	58308321	58309557	−	SCARNA20	0x0
2401	chr17	58448595	58449725	−	USP32	0x0
2402	chr17	58710732	58711871	+	PPM1D	0x2
2403	chr17	59275968	59277116	+	BCAS3	0x0
2404	chr17	59316760	59318001	+	BCAS3	0x0
2405	chr17	59432076	59433255	−	NACA2	0x0
2406	chr17	59821357	59822521	−	BRIP1	0x2
2407	chr17	60023113	60024212	−	MED13	0x0
2408	chr17	60086819	60087918	−	MED13	0x0
2409	chr17	60100732	60101884	−	MED13	0x0
2410	chr17	60458542	60459757	+	EFCAB3	0x0
2411	chr17	60480366	60481496	−	TBC1D3P2	0x0
2412	chr17	60555248	60556357	−	TBC1D3P2	0x0
2413	chr17	60610210	60611437	+	TLK2	0x0
2414	chr17	60641806	60643010	+	TLK2	0x0
2415	chr17	61043429	61044634	+	TANC2	0x0
2416	chr17	61554766	61555995	−	ACE	0x2
2417	chr17	61668036	61669123	+	DCAF7	0x0
2418	chr17	61706281	61707494	−	MAP3K3	0x0
2419	chr17	61799111	61800221	−	STRADA	0x0
2420	chr17	61823148	61824382	−	CCDC47	0x0
2421	chr17	61909439	61910644	−	SMARCD2	0x0
2422	chr17	62134563	62135698	−	ERN1	0x0
2423	chr17	62222870	62224324	+	SNORA76	0x0
2424	chr17	62222870	62224324	+	SNORD104	0x0
2425	chr17	62247937	62249096	−	TEX2	0x0
2426	chr17	62496606	62498485	−	DDX5	0x2
2427	chr17	62496606	62498485	−	MIR3064	0x0
2428	chr17	62496606	62498485	−	MIR5047	0x0
2429	chr17	62498499	62499684	−	DDX5	0x2
2430	chr17	62575922	62577102	−	SMURF2	0x2
2431	chr17	62942866	62944035	−	AMZ2P1	0x0
2432	chr17	64263301	64264539	+	PRKCA	0x0
2433	chr17	64436881	64438060	+	PRKCA	0x0
2434	chr17	64530427	64531606	+	PRKCA	0x0
2435	chr17	65168688	65169857	−	HELZ	0x0
2436	chr17	65292355	65293532	−	PSMD12	0x0
2437	chr17	65336211	65337416	−	PSMD12	0x0
2438	chr17	65409593	65410812	+	PITPNC1	0x0
2439	chr17	65736243	65737466	+	SNORA38B	0x0
2440	chr17	65821694	65822893	+	BPTF	0x2
2441	chr17	65849813	65851009	+	BPTF	0x2
2442	chr17	65959757	65960975	+	BPTF	0x2
2443	chr17	66015434	66016611	−	C17orf58	0x0
2444	chr17	66042188	66043393	+	KPNA2	0x0
2445	chr17	66122069	66123217	+	LOC100499466	0x0
2446	chr17	66527202	66528626	+	PRKAR1A	0x1
2447	chr17	72199262	72200454	+	RPL38	0x0
2448	chr17	72833367	72834565	+	TMEM104	0x0
2449	chr17	73029927	73031118	−	ATP5H	0x0
2450	chr17	73037405	73038494	+	KCTD2	0x0
2451	chr17	73131557	73132694	−	HN1	0x0
2452	chr17	73178426	73179605	−	SUMO2	0x0
2453	chr17	73218498	73219694	+	NUP85	0x0
2454	chr17	73227391	73228588	+	NUP85	0x0
2455	chr17	73313814	73314889	−	GRB2	0x2
2456	chr17	73455722	73456919	+	KIAA0195	0x0
2457	chr17	73773957	73775044	−	H3F3B	0x0
2458	chr17	73807721	73808921	+	UNK	0x0
2459	chr17	73895087	73896240	−	MRPL38	0x0
2460	chr17	73937435	73938595	−	ACOX1	0x0
2461	chr17	74077015	74078380	−	EXOC7	0x0
2462	chr17	74084980	74086079	−	EXOC7	0x0
2463	chr17	74086438	74087537	−	EXOC7	0x0
2464	chr17	74138610	74139786	−	RNF157	0x0
2465	chr17	74140038	74141515	−	RNF157	0x0
2466	chr17	74288029	74289169	−	QRICH2	0x0
2467	chr17	74326348	74327468	−	PRPSAP1	0x0
2468	chr17	74391748	74392886	−	UBE2O	0x2
2469	chr17	74554334	74555523	+	LOC100507246	0x0
2470	chr17	74554334	74555523	+	SNORD1C	0x0
2471	chr17	74559655	74561651	+	LOC100507246	0x0
2472	chr17	74670186	74671261	−	MXRA7	0x0
2473	chr17	74671792	74672890	−	MXRA7	0x0
2474	chr17	74731497	74732605	−	MIR636	0x0
2475	chr17	74731497	74732605	−	SRSF2	0x2
2476	chr17	75084818	75086125	+	LINC00338	0x0
2477	chr17	75084818	75086125	+	SCARNA16	0x0
2478	chr17	75084818	75086125	+	SEC14L1	0x0
2479	chr17	75157550	75158929	−	MIR4316	0x0
2480	chr17	75437613	75438794	+	SEPT9	0x2
2481	chr17	75495129	75496821	+	SEPT9	0x2
2482	chr17	75816292	75817394	+	FLJ45079	0x0
2483	chr17	76027252	76028462	+	TNRC6C	0x0
2484	chr17	76105054	76106203	+	TNRC6C	0x0
2485	chr17	76219271	76221106	+	BIRC5	0x0
2486	chr17	76396238	76397436	+	PGS1	0x0
2487	chr17	76670230	76671405	−	CYTH1	0x0
2488	chr17	76706536	76707691	−	CYTH1	0x0
2489	chr17	76810010	76811142	−	USP36	0x0
2490	chr17	76848640	76849834	−	TIMP2	0x0
2491	chr17	76968262	76969430	−	LGALS3BP	0x0
2492	chr17	76987582	76988709	−	CANT1	0x2
2493	chr17	77081695	77082911	+	ENGASE	0x0
2494	chr17	77751447	77752559	+	CBX2	0x0
2495	chr17	77908923	77910604	−	TBC1D16	0x0
2496	chr17	77911036	77912202	−	TBC1D16	0x0
2497	chr17	78079141	78080240	+	GAA	0x0
2498	chr17	78441438	78444535	−	NPTX1	0x0
2499	chr17	78518341	78519546	+	RPTOR	0x0
2500	chr17	78521208	78522403	+	RPTOR	0x0
2501	chr17	78900830	78902034	+	RPTOR	0x0
2502	chr17	79180215	79181398	−	AZI1	0x0
2503	chr17	79222243	79223442	+	C17orf89	0x0
2504	chr17	79224181	79225386	−	SLC38A10	0x0
2505	chr17	79231888	79233044	−	SLC38A10	0x0
2506	chr17	79249251	79250465	−	SLC38A10	0x0
2507	chr17	79362635	79363814	−	MIR4740	0x0
2508	chr17	79431650	79432774	+	BAHCC1	0x0
2509	chr17	79476602	79478114	−	ACTG1	0x0
2510	chr17	79480417	79481633	−	ACTG1	0x0
2511	chr17	79503071	79504238	−	C17orf70	0x0
2512	chr17	79516997	79518173	−	C17orf70	0x0
2513	chr17	79524060	79525921	−	NPLOC4	0x0
2514	chr17	79538509	79539655	−	NPLOC4	0x0
2515	chr17	79571064	79572231	−	NPLOC4	0x0
2516	chr17	79660352	79661562	+	HGS	0x0
2517	chr17	79668356	79669552	+	HGS	0x0
2518	chr17	79686704	79687912	+	SLC25A10	0x0
2519	chr17	79766882	79768094	+	GCGR	0x0
2520	chr17	79779775	79780909	−	FAM195B	0x0
2521	chr17	79785791	79787099	−	FAM195B	0x0
2522	chr17	79800553	79801723	−	P4HB	0x0
2523	chr17	79802990	79804345	−	P4HB	0x0
2524	chr17	79824534	79825654	+	ANAPC11	0x0
2525	chr17	79839418	79840516	−	ALYREF	0x0
2526	chr17	79842416	79844483	−	ALYREF	0x0
2527	chr17	79845379	79846425	−	ALYREF	0x0
2528	chr17	79851805	79853110	+	ANAPC11	0x0
2529	chr17	79872229	79873547	−	SIRT7	0x0
2530	chr17	79957605	79958704	+	ASPSCR1	0x0
2531	chr17	79990233	79991418	+	RAC3	0x0
2532	chr17	80007055	80008185	−	RFNG	0x0
2533	chr17	80008514	80009655	−	RFNG	0x0
2534	chr17	80020966	80022173	−	DUS1L	0x0
2535	chr17	80035753	80036898	−	FASN	0x0
2536	chr17	80038577	80039772	−	FASN	0x0
2537	chr17	80041094	80042193	−	FASN	0x0
2538	chr17	80048397	80049582	−	FASN	0x0
2539	chr17	80051030	80052507	−	FASN	0x0
2540	chr17	80055526	80056564	−	FASN	0x0
2541	chr17	80093530	80094678	−	CCDC57	0x0
2542	chr17	80111293	80112455	−	CCDC57	0x0
2543	chr17	80203472	80204534	−	CSNK1D	0x0
2544	chr17	80212410	80213512	−	CSNK1D	0x0
2545	chr17	80221639	80222776	−	CSNK1D	0x0
2546	chr17	80540194	80541386	+	FOXK2	0x0
2547	chr17	80552134	80553370	+	FOXK2	0x0
2548	chr17	80559523	80560801	+	FOXK2	0x0
2549	chr17	80572648	80573867	−	WDR45L	0x0
2550	chr17	80675431	80676530	+	FN3KRP	0x0
2551	chr17	80723624	80724793	+	TBCD	0x0
2552	chr17	80725741	80726938	+	TBCD	0x0
2553	chr17	80879768	80880945	+	TBCD	0x0
2554	chr17	80922711	80923915	−	B3GNTL1	0x0
2555	chr18	261064	262183	−	THOC1	0x0
2556	chr18	319122	320335	−	COLEC12	0x0
2557	chr18	421767	422978	−	COLEC12	0x0
2558	chr18	721629	722906	−	YES1	0x0
2559	chr18	759931	761128	−	YES1	0x0
2560	chr18	2380851	2382070	+	NDC80	0x2
2561	chr18	5840188	5841409	+	MIR3976	0x0
2562	chr18	6301429	6302684	−	L3MBTL4	0x1
2563	chr18	6310997	6312174	−	L3MBTL4	0x1
2564	chr18	9399920	9401153	+	TWSG1	0x0
2565	chr18	9524016	9525208	+	RALBP1	0x0
2566	chr18	9535748	9536953	+	RALBP1	0x0
2567	chr18	9569916	9571148	−	PPP4R1	0x0
2568	chr18	9710586	9711734	+	RAB31	0x0
2569	chr18	9861621	9862813	+	RAB31	0x0
2570	chr18	9953971	9955154	+	VAPA	0x0
2571	chr18	10532844	10534018	+	NAPG	0x0
2572	chr18	12309965	12311147	+	TUBB6	0x0
2573	chr18	12446096	12447328	−	SPIRE1	0x0
2574	chr18	12455237	12456416	−	SPIRE1	0x0
2575	chr18	12546141	12547368	−	SPIRE1	0x0
2576	chr18	12934265	12935389	+	SEH1L	0x0
2577	chr18	13681472	13682627	−	FAM210A	0x0
2578	chr18	19348091	19349274	+	MIB1	0x0
2579	chr18	19353015	19354226	+	MIB1	0x0
2580	chr18	19358990	19360117	+	MIB1	0x0
2581	chr18	19409262	19410364	+	MIB1	0x0
2582	chr18	19446390	19447573	+	MIB1	0x0
2583	chr18	20714978	20716166	+	CABLES1	0x1
2584	chr18	20780816	20782005	+	CABLES1	0x1
2585	chr18	21191142	21192365	+	LAMA3	0x0
2586	chr18	21938451	21939627	−	OSBPL1A	0x0
2587	chr18	23597385	23598512	−	SS18	0x0
2588	chr18	29204767	29205899	−	B4GALT6	0x0
2589	chr18	29298411	29299551	+	TTR	0x0
2590	chr18	29451847	29452976	−	TRAPPC8	0x0
2591	chr18	29691209	29692408	+	RNF138	0x0
2592	chr18	31433808	31435029	−	NOL4	0x0
2593	chr18	31608188	31609387	−	ASXL3	0x0
2594	chr18	32470630	32471818	+	DTNA	0x2
2595	chr18	33571402	33572486	−	RPRD1A	0x0
2596	chr18	33594761	33595888	−	RPRD1A	0x0
2597	chr18	34478931	34480136	+	KIAA1328	0x0
2598	chr18	34701645	34702810	+	KIAA1328	0x0
2599	chr18	36880605	36881780	−	LOC647946	0x0
2600	chr18	37308446	37309672	−	LOC647946	0x0
2601	chr18	37324791	37325970	−	LOC647946	0x0
2602	chr18	42374366	42375584	−	SETBP1	0x0
2603	chr18	43668976	43670384	−	ATP5A1	0x0
2604	chr18	43671168	43672337	−	ATP5A1	0x0
2605	chr18	43953766	43954965	+	RNF165	0x0
2606	chr18	45422404	45423676	−	SMAD2	0x1
2607	chr18	47015074	47016220	−	RPL17	0x0
2608	chr18	47015074	47016220	−	RPL17-C18ORF32	0x0
2609	chr18	47015074	47016220	−	SNORD58C	0x0
2610	chr18	47017102	47018645	−	RPL17	0x0
2611	chr18	47017102	47018645	−	RPL17-C18ORF32	0x0
2612	chr18	47017102	47018645	−	SNORD58A	0x0
2613	chr18	47017102	47018645	−	SNORD58B	0x0
2614	chr18	47340026	47341285	+	SCARNA17	0x0
2615	chr18	48558068	48559169	+	SMAD4	0x1
2616	chr18	48702628	48703803	−	MEX3C	0x0
2617	chr18	51748117	51749303	−	SNORA37	0x0
2618	chr18	54269694	54270879	−	TXNL1	0x0
2619	chr18	54433380	54434591	+	WDR7	0x0
2620	chr18	55143632	55144824	+	ONECUT2	0x0
2621	chr18	55150433	55151555	+	ONECUT2	0x0
2622	chr18	55269173	55270333	−	NARS	0x0
2623	chr18	56806600	56807800	+	SEC11C	0x0
2624	chr18	56995198	56996412	−	LMAN1	0x0
2625	chr18	60865174	60866368	−	BCL2	0x2
2626	chr18	60997925	60999189	−	KDSR	0x0
2627	chr18	61056709	61057890	−	VPS4B	0x0
2628	chr18	65183056	65184215	−	DSEL	0x0
2629	chr18	66525652	66526789	+	CCDC102B	0x0
2630	chr18	67140788	67141996	+	DOK6	0x0
2631	chr18	68179463	68180631	+	SOCS6	0x0
2632	chr18	71958541	71959718	−	CYB5A	0x0
2633	chr18	72370379	72371580	+	ZNF407	0x2
2634	chr18	72673866	72675068	+	ZNF407	0x2
2635	chr18	74153275	74154425	−	ZNF516	0x0
2636	chr18	77169917	77171163	+	NFATC1	0x0
2637	chr18	77226859	77228067	+	NFATC1	0x0
2638	chr18	77740134	77741271	−	TXNL4A	0x0
2639	chr18	77772388	77773636	+	RBFA	0x0
2640	chr18	77869933	77871914	+	ADNP2	0x0
2641	chr19	433713	434965	−	SHC2	0x0
2642	chr19	572067	573237	+	BSG	0x0
2643	chr19	582401	583822	+	BSG	0x0
2644	chr19	647243	648413	−	RNF126	0x0
2645	chr19	660054	661181	−	RNF126	0x0
2646	chr19	738533	739809	+	PALM	0x0
2647	chr19	797449	798548	+	PTBP1	0x0
2648	chr19	807100	808347	+	PTBP1	0x0
2649	chr19	811324	812518	+	PTBP1	0x0
2650	chr19	863453	864557	−	MED16	0x0
2651	chr19	864586	865775	−	MED16	0x0
2652	chr19	876524	877713	−	MED16	0x0
2653	chr19	896103	897244	−	R3HDM4	0x0
2654	chr19	916775	917954	+	KISS1R	0x0
2655	chr19	974159	975320	+	ARID3A	0x0
2656	chr19	1009824	1010928	−	C19orf6	0x0
2657	chr19	1087248	1088492	−	POLR2E	0x0
2658	chr19	1106011	1107109	+	GPX4	0x0
2659	chr19	1144281	1145432	−	SBNO2	0x0
2660	chr19	1159004	1160170	−	SBNO2	0x0
2661	chr19	1231861	1233081	−	C19orf26	0x0
2662	chr19	1252042	1253161	−	C19orf26	0x0
2663	chr19	1258064	1259192	+	MIDN	0x0
2664	chr19	1271892	1273420	+	CIRBP	0x0
2665	chr19	1383048	1384244	+	NDUFS7	0x0
2666	chr19	1408226	1409407	+	DAZAP1	0x0
2667	chr19	1576222	1578329	−	MBD3	0x0
2668	chr19	1584613	1587222	−	MBD3	0x0
2669	chr19	1591066	1592308	−	MBD3	0x0
2670	chr19	1609021	1611339	−	TCF3	0x2
2671	chr19	1852619	1853804	−	KLF16	0x0
2672	chr19	1985081	1986305	−	BTBD2	0x0
2673	chr19	2037117	2039388	−	MKNK2	0x0
2674	chr19	2194712	2195943	+	DOT1L	0x0
2675	chr19	2206903	2208036	+	DOT1L	0x0
2676	chr19	2230429	2232621	+	DOT1L	0x0
2677	chr19	2232946	2234118	−	MIR1227	0x0
2678	chr19	2232946	2234118	−	PLEKHJ1	0x0
2679	chr19	2248798	2250016	+	AMH	0x1
2680	chr19	2271337	2273780	+	OAZ1	0x0
2681	chr19	2323614	2324827	−	LSM7	0x0
2682	chr19	2327666	2328831	−	LSM7	0x0
2683	chr19	2426336	2427443	−	TIMM13	0x0
2684	chr19	2428253	2431164	−	LMNB2	0x0
2685	chr19	2754228	2756106	−	SGTA	0x0
2686	chr19	3023431	3024607	−	TLE2	0x0
2687	chr19	3121993	3123177	+	GNA11	0x2
2688	chr19	3208205	3209304	+	NCLN	0x0
2689	chr19	3434561	3435750	+	NFIC	0x0
2690	chr19	3621899	3623077	−	C19orf29	0x0
2691	chr19	3660460	3661587	−	PIP5K1C	0x0
2692	chr19	3975699	3978729	−	EEF2	0x0
2693	chr19	3978771	3979956	−	EEF2	0x0
2694	chr19	3980845	3983477	−	EEF2	0x0
2695	chr19	3980845	3983477	−	SNORD37	0x0
2696	chr19	4027433	4028579	+	PIAS4	0x0
2697	chr19	4034724	4035823	+	PIAS4	0x0
2698	chr19	4047304	4048448	−	ZBTB7A	0x0
2699	chr19	4055272	4056464	−	ZBTB7A	0x0
2700	chr19	4062229	4063364	−	ZBTB7A	0x0
2701	chr19	4101878	4102995	−	MAP2K2	0x0
2702	chr19	4110028	4111458	−	MAP2K2	0x0
2703	chr19	4116961	4118119	−	MAP2K2	0x0
2704	chr19	4310496	4311645	+	FSD1	0x0
2705	chr19	4322332	4323445	+	FSD1	0x0
2706	chr19	4359894	4360966	−	SH3GL1	0x2
2707	chr19	4366582	4367670	−	SH3GL1	0x2
2708	chr19	4429995	4431094	+	CHAF1A	0x0
2709	chr19	4440953	4442054	+	CHAF1A	0x0
2710	chr19	4561124	4562302	−	SEMA6B	0x0
2711	chr19	4654640	4655802	+	TNFAIP8L1	0x0
2712	chr19	4657317	4658465	−	C19orf10	0x0
2713	chr19	4917576	4918740	+	UHRF1	0x0
2714	chr19	4939459	4940559	+	UHRF1	0x0
2715	chr19	4944246	4945392	+	UHRF1	0x0
2716	chr19	4985938	4987096	+	KDM4B	0x0
2717	chr19	5046939	5048139	+	KDM4B	0x0
2718	chr19	5133469	5134656	+	KDM4B	0x0
2719	chr19	5134771	5135966	+	KDM4B	0x0
2720	chr19	5205586	5206716	−	PTPRS	0x2
2721	chr19	5266837	5267994	−	PTPRS	0x2
2722	chr19	5273735	5274901	−	PTPRS	0x2
2723	chr19	5325308	5326490	−	PTPRS	0x2
2724	chr19	5336090	5337290	−	PTPRS	0x2
2725	chr19	5566085	5567294	−	PLAC2	0x0
2726	chr19	5652831	5654001	+	SAFB	0x1
2727	chr19	5667676	5668949	+	SAFB	0x1
2728	chr19	5667701	5668881	−	C19orf70	0x0
2729	chr19	5679163	5680303	−	C19orf70	0x0
2730	chr19	5689972	5692190	+	RPL36	0x0
2731	chr19	5709498	5710708	−	LONP1	0x0
2732	chr19	5805513	5806703	+	NRTN	0x0
2733	chr19	6012390	6013607	−	RFX2	0x2
2734	chr19	6210117	6211258	−	MLLT1	0x2
2735	chr19	6211446	6213296	−	MLLT1	0x2
2736	chr19	6221935	6223135	−	MLLT1	0x2
2737	chr19	6413133	6415362	−	KHSRP	0x2
2738	chr19	6453951	6455214	−	SLC25A23	0x0
2739	chr19	6493985	6495204	−	TUBB4A	0x0
2740	chr19	7114169	7115339	−	INSR	0x0
2741	chr19	7124438	7125655	−	INSR	0x0
2742	chr19	7988914	7990981	−	CTXN1	0x0
2743	chr19	7991707	7992856	−	TIMM44	0x0
2744	chr19	8024767	8025863	−	ELAVL1	0x0
2745	chr19	8026719	8028012	−	ELAVL1	0x0
2746	chr19	8468497	8469678	+	RAB11B	0x0
2747	chr19	8553318	8554417	+	HNRNPM	0x0
2748	chr19	9680260	9681437	−	ZNF121	0x0
2749	chr19	9784612	9785787	−	ZNF562	0x0
2750	chr19	9937238	9938414	−	FBXL12	0x0
2751	chr19	9938053	9939209	+	UBL5	0x0
2752	chr19	9950227	9951326	+	PIN1	0x0
2753	chr19	10217776	10218974	+	PPAN	0x0
2754	chr19	10217776	10218974	+	PPAN-P2RY11	0x0
2755	chr19	10217776	10218974	+	SNORD105	0x0
2756	chr19	10227061	10228280	−	EIF3G	0x0
2757	chr19	10243711	10244899	−	DNMT1	0x4
2758	chr19	10250997	10252088	−	DNMT1	0x4
2759	chr19	10369710	10370861	+	MRPL4	0x0
2760	chr19	10421479	10422676	−	FDX1L	0x0
2761	chr19	10427503	10428656	−	RAVER1	0x0
2762	chr19	10463325	10464506	−	TYK2	0x0
2763	chr19	10501355	10502667	−	CDC37	0x0
2764	chr19	10777886	10779078	+	ILF3	0x0
2765	chr19	10795337	10796433	+	ILF3	0x0
2766	chr19	10800973	10802039	+	ILF3	0x0
2767	chr19	11032246	11033452	+	CARM1	0x0
2768	chr19	11082469	11083677	+	SMARCA4	0x1
2769	chr19	11107671	11108841	+	SMARCA4	0x1
2770	chr19	11133693	11134778	+	SMARCA4	0x1
2771	chr19	11223722	11224919	+	LDLR	0x0
2772	chr19	11257228	11258356	−	SPC24	0x0
2773	chr19	11455424	11456815	−	TMEM205	0x0
2774	chr19	11474649	11475822	+	LPPR2	0x0
2775	chr19	11518907	11520144	+	PRKCSH	0x0
2776	chr19	11546281	11547487	+	PRKCSH	0x0
2777	chr19	11560498	11562101	+	PRKCSH	0x0
2778	chr19	11663922	11665073	−	ELOF1	0x0
2779	chr19	11925496	11926700	+	ZNF440	0x0
2780	chr19	12698834	12699974	−	ZNF490	0x0
2781	chr19	12809813	12812031	−	TNPO2	0x0
2782	chr19	12813855	12815063	−	TNPO2	0x0
2783	chr19	12821562	12822732	−	TNPO2	0x0
2784	chr19	12825352	12826594	−	TNPO2	0x0
2785	chr19	12840942	12842171	−	C19orf43	0x0
2786	chr19	13038666	13039865	−	FARSA	0x0
2787	chr19	13040558	13041695	−	FARSA	0x0
2788	chr19	13054508	13055694	+	CALR	0x2
2789	chr19	13135373	13136566	+	NFIX	0x0
2790	chr19	13219864	13221182	−	TRMT1	0x0
2791	chr19	13229656	13230815	+	NACC1	0x0
2792	chr19	13249505	13250603	+	NACC1	0x0
2793	chr19	13264394	13265575	+	IER2	0x0
2794	chr19	13883248	13884372	+	MRI1	0x0
2795	chr19	13923224	13924434	+	ZSWIM4	0x0
2796	chr19	14198159	14199558	−	SAMD1	0x0
2797	chr19	14200909	14202105	−	SAMD1	0x0
2798	chr19	14293844	14294997	−	LPHN1	0x2
2799	chr19	14579728	14580828	+	PKN1	0x2
2800	chr19	14581976	14583102	+	PKN1	0x2
2801	chr19	14588668	14589819	−	GIPC1	0x0
2802	chr19	14625659	14625906	−	DNAJB1	0x0
2803	chr19	14732536	14733997	+	CLEC17A	0x0
2804	chr19	15270591	15271715	−	NOTCH3	0x0
2805	chr19	15465179	15466371	−	AKAP8	0x2
2806	chr19	15468886	15470088	−	AKAP8	0x2
2807	chr19	15513523	15514703	−	AKAP8L	0x0
2808	chr19	16212928	16214130	+	TPM4	0x0
2809	chr19	16345227	16346378	+	AP1M1	0x0
2810	chr19	16376027	16377201	−	CIB3	0x0
2811	chr19	16470042	16471169	−	EPS15L1	0x0
2812	chr19	16651975	16653236	−	CHERP	0x0
2813	chr19	16737773	16738944	−	MED26	0x0
2814	chr19	16790289	16791467	+	TMEM38A	0x0
2815	chr19	17212335	17213596	+	MYO9B	0x0
2816	chr19	17391547	17392710	+	ANKLE1	0x0
2817	chr19	17416651	17417847	+	MRPL34	0x0
2818	chr19	17692166	17693768	+	GLT25D1	0x0
2819	chr19	17874502	17875704	+	FCHO1	0x0
2820	chr19	17972879	17974106	+	RPL18A	0x0
2821	chr19	17972879	17974106	+	SNORA68	0x0
2822	chr19	18245096	18246253	+	MAST3	0x0
2823	chr19	18390080	18391372	−	JUND	0x0
2824	chr19	18418226	18419383	−	LSM4	0x0
2825	chr19	18546682	18547816	−	ISYNA1	0x0
2826	chr19	18649873	18651098	−	FKBP8	0x0
2827	chr19	18652180	18653326	−	FKBP8	0x0
2828	chr19	18679220	18680543	+	KXD1	0x0
2829	chr19	18884271	18885435	+	CRTC1	0x2
2830	chr19	19035880	19037084	+	DDX49	0x0
2831	chr19	19108089	19109247	−	SUGP2	0x0
2832	chr19	19120195	19121638	−	SUGP2	0x0
2833	chr19	19152147	19153382	+	ARMC6	0x0
2834	chr19	19170255	19171474	+	ARMC6	0x0
2835	chr19	19246414	19248580	−	TMEM161A	0x0
2836	chr19	19407380	19408591	−	SUGP1	0x0
2837	chr19	19515851	19517059	+	GATAD2A	0x0
2838	chr19	19565218	19566440	+	GATAD2A	0x0
2839	chr19	19606355	19607510	+	GATAD2A	0x0
2840	chr19	19618774	19619862	+	GATAD2A	0x0
2841	chr19	19641808	19642907	+	YJEFN3	0x0
2842	chr19	19709318	19710495	−	PBX4	0x0
2843	chr19	21207859	21209170	+	ZNF430	0x0
2844	chr19	21289831	21291024	+	ZNF714	0x0
2845	chr19	22877044	22878262	−	ZNF99	0x0
2846	chr19	24009538	24011365	+	RPSAP58	0x0
2847	chr19	24183115	24184722	−	LOC100101266	0x0
2848	chr19	30499618	30500671	+	URI1	0x0
2849	chr19	30824657	30825856	+	ZNF536	0x2
2850	chr19	33077622	33078844	+	PDCD5	0x0
2851	chr19	33188805	33189954	+	NUDT19	0x0
2852	chr19	33460137	33461317	−	CEP89	0x0
2853	chr19	33791628	33792820	−	CEBPA	0x1
2854	chr19	34304490	34305768	+	KCTD15	0x0
2855	chr19	34718119	34719264	+	LSM14A	0x0
2856	chr19	34858984	34860104	+	GPI	0x0
2857	chr19	34890809	34892921	+	GPI	0x0
2858	chr19	34925241	34926410	+	UBA2	0x0
2859	chr19	34940655	34941844	+	UBA2	0x0
2860	chr19	35503647	35504748	−	GRAMD1A	0x0
2861	chr19	35769770	35771106	+	USF2	0x0
2862	chr19	36065946	36067217	+	TMEM147	0x0
2863	chr19	36123827	36124926	+	RBM42	0x0
2864	chr19	36148991	36150113	+	COX6B1	0x0
2865	chr19	36212927	36214148	+	MLL4	0x0
2866	chr19	36582377	36583533	+	WDR62	0x0
2867	chr19	36631344	36632542	+	CAPNS1	0x0
2868	chr19	38431494	38432690	+	SIPA1L3	0x0
2869	chr19	39326617	39327844	−	HNRNPL	0x0
2870	chr19	39337434	39338533	−	HNRNPL	0x0
2871	chr19	39410724	39412282	−	SARS2	0x0
2872	chr19	39676724	39677915	+	PAK4	0x0
2873	chr19	39797108	39798331	−	LRFN1	0x0
2874	chr19	39888164	39889343	+	MED29	0x2
2875	chr19	39902265	39903407	−	MIR4530	0x0
2876	chr19	39923315	39924524	−	RPS16	0x0
2877	chr19	39976373	39977573	+	TIMM50	0x0
2878	chr19	40324585	40325684	−	DYRK1B	0x0
2879	chr19	40324585	40325684	−	FBI	0x0
2880	chr19	40697581	40698898	+	MAP3K10	0x0
2881	chr19	40738955	40740117	−	AKT2	0x2
2882	chr19	40783554	40784768	−	MIR641	0x0
2883	chr19	40784791	40786415	−	MIR641	0x0
2884	chr19	40789643	40791062	−	AKT2	0x2
2885	chr19	40821326	40822426	−	C19orf47	0x0
2886	chr19	40826618	40827833	−	C19orf47	0x0
2887	chr19	40871081	40872319	+	PLD3	0x0
2888	chr19	41307405	41308504	−	EGLN2	0x0
2889	chr19	41307405	41308504	+	RAB4B-EGLN2	0x0
2890	chr19	41313315	41314483	+	EGLN2	0x0
2891	chr19	41313315	41314483	+	RAB4B-EGLN2	0x0
2892	chr19	41784451	41785650	+	HNRNPUL1	0x0
2893	chr19	41800880	41802017	+	HNRNPUL1	0x0
2894	chr19	41812393	41813671	+	HNRNPUL1	0x0
2895	chr19	41815425	41816747	−	TGFB1	0x1
2896	chr19	41829951	41831140	−	CCDC97	0x0
2897	chr19	42069747	42070918	−	CEACAM4	0x0
2898	chr19	42364262	42365484	+	RPS19	0x0
2899	chr19	42375951	42377127	+	RPS19	0x0
2900	chr19	42751641	42752823	−	ERF	0x1
2901	chr19	42792581	42793913	+	CIC	0x2
2902	chr19	42838329	42840427	+	MEGF8	0x0
2903	chr19	42853211	42854995	+	MEGF8	0x0
2904	chr19	42881170	42882304	+	MEGF8	0x0
2905	chr19	42937196	42938377	+	MEGF8	0x0
2906	chr19	43909808	43910977	+	TEX101	0x0
2907	chr19	44046898	44048117	−	XRCC1	0x0
2908	chr19	44111103	44112238	−	ZNF428	0x0
2909	chr19	44677729	44678937	+	ZNF226	0x2
2910	chr19	45489903	45491113	+	CLPTM1	0x0
2911	chr19	45637271	45638417	+	PPP1R37	0x0
2912	chr19	45981284	45982504	−	RTN2	0x0
2913	chr19	46055463	46056676	−	OPA3	0x0
2914	chr19	46191155	46192341	−	SNRPD2	0x0
2915	chr19	46285399	46290500	−	DMPK	0x0
2916	chr19	46285399	46290500	−	DMWD	0x0
2917	chr19	46361925	46363145	+	FOXA3	0x0
2918	chr19	45403964	46405141	−	MYPOP	0x0
2919	chr19	46441853	46443027	−	NOVA2	0x0
2920	chr19	47112545	47113889	+	CALM3	0x0
2921	chr19	47219629	47220775	−	PRKD2	0x0
2922	chr19	47230409	47231590	−	STRN4	0x0
2923	chr19	47234518	47235724	−	STRN4	0x0
2924	chr19	47277768	47279296	−	SLC1A5	0x0
2925	chr19	47287026	47288125	−	SLC1A5	0x0
2926	chr19	47290828	47292007	−	SLC1A5	0x0
2927	chr19	47421491	47422610	+	ARHGAP35	0x1
2928	chr19	47505828	47507452	+	ARHGAP35	0x1
2929	chr19	47571603	47572761	−	ZC3H4	0x0
2930	chr19	47633618	47634854	+	SAE1	0x0
2931	chr19	47857790	47859035	+	DHX34	0x0
2932	chr19	47884204	47885407	+	DHX34	0x0
2933	chr19	47995135	47996311	−	NAPA	0x0
2934	chr19	48179700	48180894	+	GLTSCR1	0x1
2935	chr19	48258914	48260113	+	GLTSCR2	0x1
2936	chr19	48258914	48260113	+	SNORD23	0x0
2937	chr19	48287091	48288282	+	SEPW1	0x0
2938	chr19	48426524	48427748	+	SNAR-A10	0x0
2939	chr19	48426524	48427748	+	SNAR-A11	0x0
2940	chr19	48426524	48427748	+	SNAR-A14	0x0
2941	chr19	48426524	48427748	+	SNAR-A3	0x0
2942	chr19	48426524	48427748	+	SNAR-A4	0x0
2943	chr19	48426524	48427748	+	SNAR-A5	0x0
2944	chr19	48426524	48427748	+	SNAR-A6	0x0
2945	chr19	48426524	48427748	+	SNAR-A7	0x0
2946	chr19	48426524	48427748	+	SNAR-A8	0x0
2947	chr19	48426524	48427748	+	SNAR-A9	0x0
2948	chr19	48638772	48639948	−	LIG1	0x0
2949	chr19	48640427	48641526	−	LIG1	0x0
2950	chr19	48642529	48643725	−	LIG1	0x0
2951	chr19	48704862	48706055	−	CARD8	0x0
2952	chr19	48885682	48886906	−	KDELR1	0x0
2953	chr19	48893193	48894425	−	KDELR1	0x0
2954	chr19	49118619	49120644	−	RPL18	0x0
2955	chr19	49297824	49298967	−	BCAT2	0x0
2956	chr19	49303599	49304778	−	BCAT2	0x0
2957	chr19	49425423	49426724	+	NUCB1	0x0
2958	chr19	49469028	49470166	+	FTL	0x0
2959	chr19	49471950	49473128	−	GYS1	0x0
2960	chr19	49588237	49589435	+	SNRNP70	0x0
2961	chr19	49592075	49593223	+	SNRNP70	0x0
2962	chr19	49607258	49608427	+	SNRNP70	0x0
2963	chr19	49645121	49646312	+	PPFIA3	0x0
2964	chr19	49670843	49672015	+	TRPM4	0x0
2965	chr19	49863523	49864822	−	TEAD2	0x0
2966	chr19	49955965	49957142	+	ALDH16A1	0x0
2967	chr19	49992705	49993802	+	RPL13A	0x0
2968	chr19	49992705	49993802	+	RPL13AP5	0x0
2969	chr19	49992705	49993802	+	SNORD32A	0x0
2970	chr19	49994537	49995624	+	RPL13A	0x0
2971	chr19	49994537	49995624	+	RPL13AP5	0x0
2972	chr19	50000608	50001855	+	RPS11	0x0
2973	chr19	50000608	50001855	+	SNORD35B	0x0
2974	chr19	50002222	50003374	+	RPS11	0x0
2975	chr19	50028948	50030116	+	FCGRT	0x0
2976	chr19	50098847	50100070	−	PRR12	0x0
2977	chr19	50104606	50105797	+	PRR12	0x0
2978	chr19	50125677	50126919	+	PRR12	0x0
2979	chr19	50359518	50362672	−	PTOV1	0x0
2980	chr19	50409664	50411091	−	NUP62	0x0
2981	chr19	52381165	52382302	−	ZNF577	0x0
2982	chr19	52729015	52730190	+	PPP2R1A	0x2
2983	chr19	53226284	53227434	−	ZNF611	0x0
2984	chr19	54462756	54463932	+	CACNG8	0x0
2985	chr19	54605893	54607047	+	NDUFA3	0x0
2986	chr19	54704517	54705652	+	RPS9	0x0
2987	chr19	54710900	54712000	+	RPS9	0x0
2988	chr19	54969341	54970479	+	LENG8	0x0
2989	chr19	54972309	54973633	+	LENG8	0x0
2990	chr19	55559299	55560476	−	RDH13	0x0
2991	chr19	55897400	55898599	+	RPL28	0x0
2992	chr19	55899145	55900296	+	RPL28	0x0
2993	chr19	55900600	55901783	+	RPL28	0x0
2994	chr19	55945818	55947059	+	ZNF628	0x0
2995	chr19	55978495	55979717	+	ZNF628	0x0
2996	chr19	55997742	55999096	+	NAT14	0x0
2997	chr19	56090628	56091988	−	ZNF579	0x0
2998	chr19	56172904	56173985	+	U2AF2	0x2
2999	chr19	56185234	56186475	+	U2AF2	0x2
3000	chr19	56667669	56668775	+	ZNF444	0x0
3001	chr19	57725909	57727008	+	ZNF264	0x4
3002	chr19	57910640	57911792	+	ZNF548	0x0
3003	chr19	57973839	57975442	−	ZNF772	0x0
3004	chr19	57979307	57980462	−	ZNF772	0x0
3005	chr19	58217480	58218587	+	ZNF551	0x0
3006	chr19	58280064	58281258	+	ZNF586	0x0
3007	chr19	58295632	58296837	+	ZNF586	0x0
3008	chr19	58378068	58379253	+	ZNF587	0x0
3009	chr19	58455718	58456894	−	ZNF256	0x0
3010	chr19	58874297	58875496	+	A1BG-AS1	0x0
3011	chr19	58904215	58905433	+	RPS5	0x0
3012	chr19	59024596	59025774	−	ZBTB45	0x0
3013	chr19	59061179	59062583	+	TRIM28	0x0
3014	chr19	59066969	59068097	−	UBE2M	0x0
3015	chr19	59069120	59070278	−	UBE2M	0x0
3016	chr2	1216356	1217585	+	SNTG2	0x0
3017	chr2	1636731	1637920	−	PXDN	0x2
3018	chr2	2363834	2365034	−	MYTH	0x0
3019	chr2	3320034	3321188	−	TSSC1	0x0
3020	chr2	8869616	8870757	−	KIDINS220	0x0
3021	chr2	8994807	8995934	−	MBOAT2	0x0
3022	chr2	8997799	8999023	−	MBOAT2	0x0
3023	chr2	9757076	9758210	−	YWHAQ	0x2
3024	chr2	10586337	10587409	−	SNORA80B	0x0
3025	chr2	11724384	11725662	+	GREB1	0x0
3026	chr2	11906920	11908110	+	LPIN1	0x0
3027	chr2	15653200	15654333	−	NBAS	0x0
3028	chr2	16639823	16641013	+	MYCN	0x2
3029	chr2	17942106	17943268	+	GEN1	0x2
3030	chr2	20232436	20233529	−	LAPTM4A	0x0
3031	chr2	20417746	20419143	−	SDC1	0x0
3032	chr2	20501494	20502666	−	PUM2	0x0
3033	chr2	20680167	20681308	+	RHOB	0x1
3034	chr2	23629735	23630885	+	KLHL29	0x0
3035	chr2	23644452	23645882	+	KLHL29	0x0
3036	chr2	23675495	23676607	+	KLHL29	0x0
3037	chr2	24079710	24080888	−	ATAD2B	0x0
3038	chr2	24289952	24291126	−	SF3B14	0x0
3039	chr2	25004382	25005586	+	CENPO	0x0
3040	chr2	25452998	25454097	−	DNMT3A	0x2
3041	chr2	25961435	25962615	−	ASXL2	0x0
3042	chr2	26250444	26251731	−	KIF3C	0x0
3043	chr2	26256446	26257646	+	RAB10	0x0
3044	chr2	26617976	26619180	+	EPT1	0x0
3045	chr2	27273066	27274339	+	AGBL5	0x0
3046	chr2	27355797	27356988	−	PREB	0x0
3047	chr2	27456383	27457481	+	CAD	0x0
3048	chr2	27477080	27478216	−	SLC30A3	0x0
3049	chr2	28974355	28975566	+	PPP1CB	0x0
3050	chr2	29135977	29137186	+	SNORD92	0x0
3051	chr2	29135977	29137186	+	WDR43	0x0
3052	chr2	29148700	29149881	+	WDR43	0x0
3053	chr2	29150294	29151499	+	WDR43	0x0
3054	chr2	29388281	29389489	+	CLIP4	0x0
3055	chr2	30723323	30724519	+	LCLAT1	0x0
3056	chr2	32140854	32141953	−	MEMO1	0x0
3057	chr2	32248479	32249699	−	DPY30	0x0
3058	chr2	33726765	33727887	+	RASGRP3	0x0
3059	chr2	33739891	33741064	−	FAM98A	0x0
3060	chr2	35845713	35846891	−	LOC100288911	0x0
3061	chr2	36667962	36669182	+	CRIM1	0x0
3062	chr2	36669204	36670402	+	CRIM1	0x0
3063	chr2	37080343	37081493	−	STRN	0x0
3064	chr2	37326947	37328278	−	EIF2AK2	0x1
3065	chr2	37332097	37333466	−	EIF2AK2	0x1
3066	chr2	38708654	38710070	+	GALM	0x0
3067	chr2	39220563	39221718	−	SOS1	0x2
3068	chr2	39281328	39282494	−	SOS1	0x2
3069	chr2	40424638	40425802	−	SLC8A1	0x0
3070	chr2	40655162	40656518	−	SLC8A1	0x0
3071	chr2	42417346	42418501	+	EML4	0x2
3072	chr2	42469322	42470470	+	EML4	0x2
3073	chr2	42930426	42931526	+	MTA3	0x0
3074	chr2	42991030	42992261	+	MTA3	0x0
3075	chr2	43628334	43629550	+	LOC100129726	0x0
3076	chr2	43707207	43708335	−	THADA	0x0
3077	chr2	43753054	43754275	−	THADA	0x0
3078	chr2	44127543	44128682	−	LRPPRC	0x0
3079	chr2	44133422	44134551	−	LRPPRC	0x0
3080	chr2	44428084	44429242	+	PPM1B	0x0
3081	chr2	44588997	44590196	+	CAMKMT	0x0
3082	chr2	44842666	44843896	+	CAMKMT	0x0
3083	chr2	45704492	45705671	−	SRBD1	0x0
3084	chr2	45789231	45790428	−	SRBD1	0x0
3085	chr2	46113133	46114336	+	PRKCE	0x0
3086	chr2	47387070	47388219	−	CALM2	0x0
3087	chr2	47389236	47390372	−	CALM2	0x0
3088	chr2	47401791	47404187	−	CALM2	0x0
3089	chr2	54084744	54085904	+	ERLEC1	0x0
3090	chr2	55198969	55200096	−	RTN4	0x0
3091	chr2	55209139	55210248	−	RTN4	0x0
3092	chr2	55276912	55278085	−	RTN4	0x0
3093	chr2	55455389	55456529	−	C2orf63	0x0
3094	chr2	55460782	55461826	+	MIR4426	0x0
3095	chr2	55460782	55461826	+	RPS27A	0x0
3096	chr2	56256982	56258160	−	MIR216B	0x0
3097	chr2	58426661	58427856	−	FANCL	0x0
3098	chr2	60775743	60776943	+	PAPOLG	0x0
3099	chr2	61105229	61106424	+	REL	0x2
3100	chr2	61129741	61130952	+	REL	0x2
3101	chr2	61152233	61153452	+	REL	0x2
3102	chr2	61441647	61442807	−	USP34	0x0
3103	chr2	61718705	61720082	−	XPO1	0x2
3104	chr2	61729986	61731165	−	XPO1	0x2
3105	chr2	61764394	61765670	−	XPO1	0x2
3106	chr2	61891926	61893148	+	COMMD1	0x4
3107	chr2	62109913	62111078	−	CCT4	0x0
3108	chr2	63185727	63186942	+	EHBP1	0x0
3109	chr2	65496944	65498205	+	ACTR2	0x0
3110	chr2	65629603	65630801	−	SPRED2	0x0
3111	chr2	69266676	69267880	+	ANTXR1	0x0
3112	chr2	69977480	69978670	+	ANXA4	0x0
3113	chr2	69998942	70000138	+	ANXA4	0x0
3114	chr2	70065682	70066781	+	GMCL1	0x0
3115	chr2	70130919	70132148	+	SNRNP27	0x0
3116	chr2	70166448	70167626	−	ASPRV1	0x0
3117	chr2	70439959	70441087	−	TIA1	0x0
3118	chr2	70451212	70453245	−	TIA1	0x0
3119	chr2	70462729	70463934	−	TIA1	0x0
3120	chr2	70475116	70476306	−	TIA1	0x0
3121	chr2	70506910	70508076	+	PCYOX1	0x0
3122	chr2	71605045	71606241	+	2NF638	0x2
3123	chr2	71660699	71661885	+	ZNF638	0x2
3124	chr2	72403769	72404907	−	EXOC6B	0x0
3125	chr2	72880523	72881715	−	EXOC6B	0x0
3126	chr2	73314836	73316011	−	RAB11F1P5	0x0
3127	chr2	73466265	73467475	+	CCT7	0x0
3128	chr2	73471196	73472298	+	CCT7	0x0
3129	chr2	74379504	74380719	−	MOB1A	0x1
3130	chr2	74472451	74473668	−	SLC4A5	0x0
3131	chr2	74604733	74605908	−	DCTN1	0x0
3132	chr2	74651919	74653107	+	WDR54	0x0
3133	chr2	74719416	74720610	+	TTC31	0x0
3134	chr2	74756938	74758134	+	HTRA2	0x1
3135	chr2	75886605	75887676	+	MRPL19	0x0
3136	chr2	76671803	76673078	−	LRRTM4	0x0
3137	chr2	78928161	78929528	+	REG3G	0x0
3138	chr2	82813926	82815121	+	LOC1720	0x0
3139	chr2	85547533	85548789	−	TGOLN2	0x0
3140	chr2	85549172	85550284	−	TGOLN2	0x0
3141	chr2	85571106	85572305	−	RETSAT	0x0
3142	chr2	85596349	85597520	+	ELMOD3	0x0
3143	chr2	85768172	85769384	+	MAT2A	0x0
3144	chr2	85770203	85771928	+	MAT2A	0x0
3145	chr2	86362432	86363688	+	PTCD3	0x0
3146	chr2	86362432	86363688	+	SNORD94	0x0
3147	chr2	96850183	96852632	−	STARD7	0x0
3148	chr2	96873373	96874629	−	STARD7	0x0
3149	chr2	96886991	96888202	+	LOC285033	0x0
3150	chr2	96917577	96918862	−	TMEM127	0x1
3151	chr2	96934086	96935241	−	TMEM127	0x1
3152	chr2	96934811	96935966	+	CIAO1	0x0
3153	chr2	96939147	96940246	+	CIAO1	0x0
3154	chr2	96964067	96965248	−	SNRNP200	0x0
3155	chr2	97028996	97030194	+	NCAPH	0x0
3156	chr2	97271741	97273016	−	KANSL3	0x0
3157	chr2	97504664	97505839	−	ANKRD23	0x0
3158	chr2	97528436	97529590	−	SEMA4C	0x0
3159	chr2	97532383	97533489	−	SEMA4C	0x0
3160	chr2	97688627	97689804	−	FAM178B	0x0
3161	chr2	97830818	97832001	+	ANKRD36	0x0
3162	chr2	98443952	98445069	+	ZAP70	0x0
3163	chr2	98611751	98612927	+	VWA3B	0x0
3164	chr2	99213766	99214929	−	COA5	0x0
3165	chr2	99327874	99329169	−	MGAT4A	0x0
3166	chr2	100505174	100506343	−	AFF3	0x2
3167	chr2	101621869	101623334	+	RPL31	0x0
3168	chr2	101634848	101636020	+	RPL31	0x0
3169	chr2	101753040	101754214	−	TBC1D8	0x0
3170	chr2	101914253	101915427	−	RNF149	0x0
3171	chr2	102471880	102473077	+	MAP4K4	0x2
3172	chr2	105470160	105471496	+	POU3F3	0x0
3173	chr2	105546628	105547807	+	POU3F3	0x0
3174	chr2	105908127	105909296	−	TGFBRAP1	0x0
3175	chr2	109182877	109184117	+	LIMS1	0x0
3176	chr2	109350228	109351366	+	RANBP2	0x0
3177	chr2	109380433	109381480	+	RANBP2	0x0
3178	chr2	111433698	111434876	−	BUB1	0x0
3179	chr2	113278429	113279578	+	TTL	0x2
3180	chr2	113288452	113289542	+	TTL	0x2
3181	chr2	113420264	113421422	+	SLC20A1	0x0
3182	chr2	114201793	114202983	+	CBWD2	0x0
3183	chr2	114567960	114569149	−	SLC35F5	0x0
3184	chr2	114708764	114709972	+	ACTR3	0x0
3185	chr2	115694554	115695736	−	LOC389023	0x0
3186	chr2	115694749	115695961	+	DPP10	0x2
3187	chr2	116999724	117000945	+	DPP10	0x2
3188	chr2	121387744	121388900	−	LOC84931	0x0
3189	chr2	121498659	121499846	+	GLI2	0x0
3190	chr2	121572475	121573681	+	GLI2	0x0
3191	chr2	121721345	121722544	+	GLI2	0x0
3192	chr2	122158585	122159790	−	CLASP1	0x0
3193	chr2	122287903	122289168	−	RNU4ATAC	0x0
3194	chr2	122326393	122327567	−	CLASP1	0x0
3195	chr2	122363177	122364331	−	CLASP1	0x0
3196	chr2	122522653	122523768	+	TSN	0x0
3197	chr2	128014354	128015560	−	ERCC3	0x2
3198	chr2	128033246	128034430	−	ERCC3	0x2
3199	chr2	128144821	128146023	−	MIR4783	0x0
3200	chr2	128263658	128264859	−	IWS1	0x0
3201	chr2	128605078	128606215	−	POLR2D	0x0
3202	chr2	128740898	128742002	−	SAP130	0x0
3203	chr2	128916619	128917760	+	UGGT1	0x2
3204	chr2	130913803	130915004	−	SMPD4	0x0
3205	chr2	130939357	130940573	+	MZT2B	0x0
3206	chr2	131094151	131095309	−	CCDC115	0x0
3207	chr2	131104509	131105707	+	IMP4	0x2
3208	chr2	131132081	131133280	+	PTPN18	0x0
3209	chr2	131805917	131807019	−	FAM168B	0x0
3210	chr2	131899453	131900659	+	PLEKHB2	0x0
3211	chr2	132245207	132246346	−	MIR4784	0x0
3212	chr2	132273057	132274242	+	LOC150776	0x0
3213	chr2	133011758	133013847	−	MIR663B	0x0
3214	chr2	133026440	133027503	−	ANKRD30BL	0x0
3215	chr2	133027871	133029879	−	ANKRD30BL	0x0
3216	chr2	133741826	133742980	−	NCKAP5	0x0
3217	chr2	134916352	134917556	+	MIR3679	0x0
3218	chr2	135211232	135212359	+	MGAT5	0x0
3219	chr2	136508474	136509745	+	UBXN4	0x0
3220	chr2	136613864	136615023	−	MCM6	0x0
3221	chr2	138786081	138787300	+	HNMT	0x0
3222	chr2	142231057	142232282	+	KYNU	0x0
3223	chr2	142246188	142247397	+	KYNU	0x0
3224	chr2	142469274	142470500	−	LRP1B	0x1
3225	chr2	142536923	142538099	−	LRP1B	0x1
3226	chr2	142742729	142743935	−	LRP1B	0x1
3227	chr2	148729810	148730961	−	ORC4	0x0
3228	chr2	149402018	149403220	+	EPC2	0x0
3229	chr2	151218773	151219905	+	LYPD6	0x0
3230	chr2	152318973	152320151	+	RIF1	0x0
3231	chr2	152802350	152803566	−	CACNB4	0x0
3232	chr2	152846132	152847415	−	CACNB4	0x0
3233	chr2	153193327	153194477	+	FMNL2	0x0
3234	chr2	153205934	153207116	+	FMNL2	0x0
3235	chr2	153524942	153526351	−	PRPF40A	0x0
3236	chr2	154729764	154730960	+	GALNT13	0x0
3237	chr2	154818140	154819320	+	GALNT13	0x0
3238	chr2	154819642	154820805	+	GALNT13	0x0
3239	chr2	155410346	155411541	+	GALNT13	0x0
3240	chr2	157033856	157035046	−	NR4A2	0x0
3241	chr2	157312157	157313327	+	GPD2	0x0
3242	chr2	158155010	158156187	−	ERMN	0x0
3243	chr2	159346768	159348023	+	PKP4	0x0
3244	chr2	160087070	160088269	+	TANC1	0x0
3245	chr2	161130286	161131453	−	RBMS1	0x0
3246	chr2	161264377	161265530	−	MIR4785	0x0
3247	chr2	162207621	162208841	+	P5MD14	0x0
3248	chr2	162979680	162980900	+	SLC4A10	0x2
3249	chr2	164457179	164458356	−	FIGN	0x0
3250	chr2	165583619	165584827	−	COBLL1	0x0
3251	chr2	166908003	166909181	−	SCN1A	0x0
3252	chr2	167036660	167037847	−	SCN9A	0x2
3253	chr2	168004968	168006187	+	XIRP2	0x2
3254	chr2	168193128	168194318	+	XIRP2	0x2
3255	chr2	168810454	168811655	−	STK39	0x0
3256	chr2	169629883	169632194	+	CERS6	0x0
3257	chr2	169708092	169709241	−	SPC25	0x0
3258	chr2	169718770	169719869	−	SPC25	0x0
3259	chr2	170745999	170747207	+	UBR3	0x2
3260	chr2	170803991	170805188	+	UBR3	0x2
3261	chr2	171822195	171823294	+	GORASP2	0x0
3262	chr2	172513412	172514608	+	DYNC1I2	0x0
3263	chr2	172964494	172965794	−	DLX2	0x0
3264	chr2	172973378	172974581	+	DLX1	0x0
3265	chr2	174812507	174813692	−	SP3	0x0
3266	chr2	175345813	175347006	−	GPR155	0x0
3267	chr2	175584480	175585720	+	SCRN3	0x0
3268	chr2	176793434	176794543	−	KIAA1715	0x0
3269	chr2	176845051	176846246	−	KIAA1715	0x0
3270	chr2	176889001	176890223	+	HOXD13	0x2
3271	chr2	177039955	177041231	−	HOXD-AS1	0x0
3272	chr2	177065262	177066455	−	HOXD-AS1	0x0
3273	chr2	178084124	178085352	+	HNRNPA3	0x0
3274	chr2	178111555	178112777	−	MIR3128	0x0
3275	chr2	178256942	178258132	+	AGPS	0x0
3276	chr2	179403300	179404432	+	LOC100506866	0x0
3277	chr2	179468434	179469583	+	LOC100506866	0x0
3278	chr2	179487035	179488248	+	LOC100506866	0x0
3279	chr2	183595170	183596369	+	DNAJC10	0x0
3280	chr2	183789780	183790961	−	NCKAP1	0x0
3281	chr2	183887963	183889156	−	NCKAP1	0x0
3282	chr2	185472545	185473764	−	ZNF804A	0x0
3283	chr2	187072084	187073267	−	ZSWIM2	0x0
3284	chr2	187167909	187169130	−	ZSWIM2	0x0
3285	chr2	187310259	187311409	−	ZSWIM2	0x0
3286	chr2	189271930	189273039	−	GULP1	0x0
3287	chr2	190317882	190319095	+	WDR75	0x0
3288	chr2	191887589	191888807	+	GLS	0x0
3289	chr2	197657125	197658291	−	GTF3C3	0x2
3290	chr2	197752015	197753239	−	PGAP1	0x0
3291	chr2	198256448	198257650	−	SF3B1	0x2
3292	chr2	198353229	198354328	−	HSPD1	0x0
3293	chr2	198367444	198368643	+	HSPE1	0x0
3294	chr2	198399765	198400920	+	HSPE1-MOB4	0x0
3295	chr2	198399765	198400920	+	MOB4	0x0
3296	chr2	200245869	200247024	−	SATB2	0x2
3297	chr2	200297611	200298794	−	SATB2	0x2
3298	chr2	201687403	201688597	+	BZW1	0x0
3299	chr2	201845865	201847050	−	FAM126B	0x0
3300	chr2	202346553	202347750	+	STRADB	0x0
3301	chr2	202485617	202487245	−	TMEM237	0x0
3302	chr2	202490564	202491687	−	TMEM237	0x0
3303	chr2	202625507	202626945	−	ALS2	0x2
3304	chr2	203157232	203158427	+	NOP58	0x0
3305	chr2	203157232	203158427	−	SNORDll	0x0
3306	chr2	203160339	203161446	+	NOP58	0x0
3307	chr2	203729600	203730792	−	ICA1L	0x0
3308	chr2	203925103	203926329	+	NBEAL1	0x0
3309	chr2	204235230	204236550	−	ABI2	0x1
3310	chr2	204293056	204294163	+	A8I2	0x1
3311	chr2	205628833	205630031	+	PARD3B	0x0
3312	chr2	206613569	206614766	+	NRP2	0x0
3313	chr2	206765021	206766246	+	NRP2	0x0
3314	chr2	206889787	206890980	+	EEF1B2	0x0
3315	chr2	206997122	206998292	−	NDUFS1	0x0
3316	chr2	207026124	207027613	+	EEF1B2	0x0
3317	chr2	207026124	207027613	+	SNORA41	0x0
3318	chr2	207026124	207027613	+	SNORD51	0x0
3319	chr2	209221075	209222274	+	PIKFYVE	0x0
3320	chr2	211512125	211513352	+	CPS1	0x2
3321	chr2	212399831	212401039	+	CPS1	0x2
3322	chr2	212428216	212429388	−	ERBB4	0x1
3323	chr2	213214823	213215916	−	MIR548F2	0x0
3324	chr2	213238740	213239938	−	MIR548F2	0x0
3325	chr2	213329050	213330269	−	MIR548F2	0x0
3326	chr2	213336293	213337490	−	MIR548F2	0x0
3327	chr2	213390114	213391313	−	ERBB4	0x1
3328	chr2	216995072	216996232	+	XRCC5	0x0
3329	chr2	217069580	217070799	+	XRCC5	0x0
3330	chr2	217363468	217365329	+	RPL37A	0x0
3331	chr2	217365531	217366649	+	RPL37A	0x0
3332	chr2	217383074	217384232	+	RPL37A	0x0
3333	chr2	217431845	217433045	+	IGFBP2	0x0
3334	chr2	217538206	217540299	−	IGFBP5	0x1
3335	chr2	218286440	218287567	−	DIRC3	0x0
3336	chr2	218400358	218401552	−	DIRC3	0x0
3337	chr2	219109965	219111160	+	ARPC2	0x0
3338	chr2	219134612	219135878	+	PNKD	0x0
3339	chr2	219365160	219366302	−	USP37	0x0
3340	chr2	219525952	219527133	+	BCS1L	0x0
3341	chr2	220047566	220048764	+	FAM134A	0x0
3342	chr2	220083700	220085128	−	ABCB6	0x0
3343	chr2	220083700	220085128	−	ATG9A	0x0
3344	chr2	220431286	220432550	−	OBSL1	0x0
3345	chr2	223084400	223085617	−	PAX3	0x2
3346	chr2	223771341	223772508	+	ACSL3	0x2
3347	chr2	225337375	225338590	−	CUL3	0x1
3348	chr2	225357124	225358316	−	CUL3	0x1
3349	chr2	225362717	225363887	−	CUL3	0x1
3350	chr2	225449421	225450594	−	CUL3	0x1
3351	chr2	228627217	228628393	−	SLC19A3	0x0
3352	chr2	230015177	230016385	+	FBXO36	0x0
3353	chr2	230723204	230724432	−	TRIP12	0x0
3354	chr2	231684657	231685792	+	CAB39	0x0
3355	chr2	231742416	231743651	+	ITM2C	0x0
3356	chr2	231895330	231896507	−	LOC348761	0x0
3357	chr2	232319052	232321792	−	NCL	0x0
3358	chr2	232319052	232321792	−	SNORA75	0x0
3359	chr2	232319052	232321792	−	SNORD20	0x0
3360	chr2	232324517	232325714	−	NCL	0x0
3361	chr2	232324517	232325714	−	SNORD82	0x0
3362	chr2	232328602	232329702	−	NCL	0x0
3363	chr2	232576047	232577235	+	PTMA	0x0
3364	chr2	233936152	233937371	+	INPP5D	0x0
3365	chr2	234183893	234185136	+	SCARNA5	0x0
3366	chr2	234196971	234198139	+	SCARNA6	0x0
3367	chr2	234379111	234380348	+	DGKD	0x0
3368	chr2	236707724	236708823	+	AGAP1	0x0
3369	chr2	237084009	237085207	+	AGAP1	0x0
3370	chr2	237828105	237829302	−	COL6A3	0x0
3371	chr2	237994178	237995402	+	COPS8	0x0
3372	chr2	238640130	238641441	+	LRRFIP1	0x2
3373	chr2	238977416	238978680	+	SCLY	0x0
3374	chr2	238977416	238978680	+	UBE2F-SCLY	0x0
3375	chr2	240566799	240567975	+	LOC150935	0x0
3376	chr2	240927842	240929122	−	NDUFA10	0x0
3377	chr2	241438874	241440090	−	ANKMY1	0x0
3378	chr2	241463023	241464122	−	ANKMY1	0x0
3379	chr2	241464673	241465805	−	ANKMY1	0x0
3380	chr2	241537146	241538345	+	CAPN10	0x0
3381	chr2	241653284	241655521	−	KIF1A	0x2
3382	chr2	241680148	241681373	−	KIF1A	0x2
3383	chr2	241696785	241697921	−	KIF1A	0x2
3384	chr2	242168371	242169557	−	HDLBP	0x2
3385	chr2	242172844	242174023	−	ANO7	0x0
3386	chr2	242254254	242255441	+	SEPT2	0x0
3387	chr2	242280235	242282090	+	SEPT2	0x0
3388	chr2	242291056	242292245	+	SEPT2	0x0
3389	chr2	242292246	242293356	+	SEPT2	0x0
3390	chr2	242434431	242435563	−	STK25	0x0
3391	chr2	242684886	242686231	−	D2HGDH	0x0
3392	chr2	242699828	242700961	+	D2HGDH	0x0
3393	chr20	308144	309463	+	SOX12	0x0
3394	chr20	463505	464699	−	CSNK2A1	0x0
3395	chr20	1161617	1162788	−	TMEM74B	0x0
3396	chr20	1349577	1351191	−	FKBP1A	0x0
3397	chr20	1918344	1919624	+	SIRPA	0x0
3398	chr20	2443060	2444241	−	SNORD119	0x0
3399	chr20	2443060	2444241	−	SNRPB	0x0
3400	chr20	2447764	2448925	−	SNRPB	0x0
3401	chr20	2635175	2636402	+	NOP56	0x0
3402	chr20	2635175	2636402	+	SNORA51	0x0
3403	chr20	2637038	2638212	+	NOP56	0x0
3404	chr20	2637038	2638212	+	SNORD56	0x0
3405	chr20	2637038	2638212	+	SNORD57	0x0
3406	chr20	3145220	3146658	−	ProSAPiP1	0x0
3407	chr20	3733763	3734862	−	C20orf27	0x0
3408	chr20	4004220	4005516	+	PANK2	0x0
3409	chr20	4152647	4153818	−	ADRA1D	0x0
3410	chr20	5060684	5061856	−	C20orf30	0x0
3411	chr20	5164963	5166161	+	CDS2	0x0
3412	chr20	6559171	6560272	+	BMP2	0x1
3413	chr20	8864641	8865840	+	PLCB1	0x0
3414	chr20	9172099	9173278	+	PLCB4	0x2
3415	chr20	11905246	11906565	+	BTBD3	0x0
3416	chr20	11972785	11974015	+	BTBD3	0x0
3417	chr20	17930389	17931587	−	SNX5	0x0
3418	chr20	17942784	17944058	−	SNORD17	0x0
3419	chr20	18245801	18247009	−	DZANK1	0x0
3420	chr20	18485060	18486248	+	SEC23B	0x0
3421	chr20	25515364	25516505	−	NINL	0x0
3422	chr20	25845882	25847080	+	LOC100134868	0x0
3423	chr20	26188218	26190630	−	LOC284801	0x0
3424	chr20	26188218	26190630	−	MIR663A	0x0
3425	chr20	29620241	29621478	+	FRG1B	0x0
3426	chr20	30373619	30374717	+	TPX2	0x0
3427	chr20	30754487	30755598	+	TM9SF4	0x0
3428	chr20	30927750	30928849	+	KIF3B	0x0
3429	chr20	30953660	30954792	+	ASXL1	0x1
3430	chr20	31379762	31380979	+	DNMT3B	0x0
3431	chr20	31436868	31438511	+	MAPRE1	0x0
3432	chr20	31940667	31941815	−	CDK5RAP1	0x0
3433	chr20	31974725	31975863	−	CDK5RAP1	0x0
3434	chr20	32263513	32264643	−	E2F1	0x1
3435	chr20	32273238	32274483	−	E2F1	0x1
3436	chr20	32867650	32868912	−	AHCY	0x0
3437	chr20	33027471	33028640	−	ITCH	0x2
3438	chr20	33361081	33362271	−	NCOA6	0x2
3439	chr20	33530007	33531300	−	GSS	0x0
3440	chr20	33610313	33611516	−	TRPC4AP	0x0
3441	chr20	33866251	33867414	−	EIF6	0x0
3442	chr20	34091229	34092435	+	CEP250	0x0
3443	chr20	34144721	34145900	+	ERGIC3	0x0
3444	chr20	34218394	34219612	+	CPNE1	0x0
3445	chr20	34233085	34234229	−	RBM12	0x0
3446	chr20	34288156	34289329	+	ROMO1	0x0
3447	chr20	34301632	34302837	−	RBM39	0x0
3448	chr20	34312012	34313213	−	RBM39	0x0
3449	chr20	34430845	34432061	+	PHF20	0x0
3450	chr20	34633445	34634576	−	LOC647979	0x0
3451	chr20	34636380	34637538	−	LOC647979	0x0
3452	chr20	35221533	35222724	+	TGIF2	0x0
3453	chr20	35281129	35282335	−	NDRG3	0x0
3454	chr20	35422398	35423497	−	KIAA0889	0x0
3455	chr20	35443437	35444575	−	KIAA0889	0x0
3456	chr20	35466846	35467976	−	KIAA0889	0x0
3457	chr20	35485069	35486168	−	KIAA0889	0x0
3458	chr20	35519588	35520734	−	SAMHD1	0x0
3459	chr20	35857418	35858593	+	RPN2	0x0
3460	chr20	36064875	36066076	−	BLCAP	0x5
3461	chr20	36145828	36146964	−	BLCAP	0x5
3462	chr20	36147195	36148377	−	BLCAP	0x5
3463	chr20	36603038	36604247	−	TTI1	0x0
3464	chr20	37047754	37049031	−	LOC388796	0x0
3465	chr20	37053360	37054538	−	SNORA71B	0x0
3466	chr20	37055441	37056553	−	SNORA71A	0x0
3467	chr20	37062007	37063212	−	LOC388796	0x0
3468	chr20	37062007	37063212	−	SNORA71D	0x0
3469	chr20	37189919	37191130	+	RALGAPB	0x0
3470	chr20	37389853	37390980	+	ACTR5	0x0
3471	chr20	37500902	37502082	+	PPP1R16B	0x0
3472	chr20	37960926	37962082	−	LOC339568	0x0
3473	chr20	39652337	39653562	+	TOP1	0x2
3474	chr20	39751537	39752686	+	TOP1	0x2
3475	chr20	39755510	39756646	+	TOP1	0x2
3476	chr20	42086469	42087562	+	SRSF6	0x2
3477	chr20	42101122	42102269	+	SRSF6	0x2
3478	chr20	42139312	42140444	−	GTSF1L	0x0
3479	chr20	42142857	42143994	+	L3MBTL1	0x0
3480	chr20	42225881	42227031	+	IFT52	0x0
3481	chr20	42320252	42321487	+	MYBL2	0x0
3482	chr20	42635354	42636553	+	TOX2	0x0
3483	chr20	43380554	43381761	−	RIMS4	0x0
3484	chr20	43535683	43536777	+	YWHAB	0x2
3485	chr20	44469990	44471179	−	ACOT8	0x0
3486	chr20	44498416	44499609	+	ZSWIM3	0x0
3487	chr20	44557368	44558519	−	PLTP	0x0
3488	chr20	45892219	45893412	−	ZMYND8	0x0
3489	chr20	47896310	47897875	+	SNORD12	0x0
3490	chr20	47896310	47897875	+	SNORD12B	0x0
3491	chr20	47896310	47897875	+	ZNFX1-AS1	0x0
3492	chr20	47964535	47965725	+	ZNFX1-AS1	0x0
3493	chr20	48288304	48289481	−	B4GALT5	0x0
3494	chr20	48697546	48698670	−	TMEM189-UBE2V1	0x0
3495	chr20	48697546	48698670	−	UBE2V1	0x0
3496	chr20	48706461	48707619	−	TMEM189-UBE2V1	0x0
3497	chr20	48706461	48707619	−	UBE2V1	0x0
3498	chr20	49541256	49542400	−	ADNP	0x0
3499	chr20	50216789	50217980	−	ATP9A	0x0
3500	chr20	50512575	50513768	−	SALL4	0x0
3501	chr20	50556896	50658253	−	ZFP64	0x2
3502	chr20	50702728	50703853	−	ZFP64	0x2
3503	chr20	50704408	50705579	−	ZFP64	0x2
3504	chr20	51687704	51688904	+	TSHZ2	0x2
3505	chr20	57022743	57023963	+	VAPB	0x0
3506	chr20	57233979	57235189	+	STX16	0x0
3507	chr20	57233979	57235189	+	STX16-NPEPL1	0x0
3508	chr20	57465380	57466479	+	GNAS	0x6
3509	chr20	57479961	57481011	+	GNAS	0x6
3510	chr20	57483814	57485692	+	GNAS	0x6
3511	chr20	57608841	57609971	−	SLMO2	0x0
3512	chr20	60513126	60514302	−	MIR1Z57	0x0
3513	chr20	60588238	60589418	−	TAF4	0x0
3514	chr20	60639005	60640133	−	TAF4	0x0
3515	chr20	60848232	60849342	+	OSBPL2	0x0
3516	chr20	60906798	60907895	−	LAMA5	0x0
3517	chr20	60906798	60907895	−	MIR4758	0x0
3518	chr20	60934764	60935941	−	LAMA5	0x0
3519	chr20	60941458	60942635	−	LAMA5	0x0
3520	chr20	60962350	60964070	+	RPS21	0x0
3521	chr20	61431286	61432436	+	C20orf20	0x4
3522	chr20	61478722	61479897	−	TCFL5	0x0
3523	chr20	61907455	61908654	+	ARFGAP1	0x0
3524	chr20	62289653	62290799	+	RTEL1	0x0
3525	chr20	62289653	62290799	+	RTEL1-TNFRSF6B	0x0
3526	chr20	62338006	62339157	−	ARFRP1	0x0
3527	chr20	62365427	62366595	+	ZGPAT	0x0
3528	chr20	62373279	62374403	+	SLC2A4RG	0x0
3529	chr20	62527170	62528378	+	DNAJC5	0x0
3530	chr20	62545422	62546619	+	MIR941-1	0x0
3531	chr20	62573549	62574693	−	MIR647	0x0
3532	chr20	62582519	62583704	−	UCKL1	0x0
3533	chr20	62599061	62600188	−	ZNF512B	0x0
3534	chr20	62612010	62613160	+	PRPF6	0x0
3535	chr21	16016413	16017631	+	ABCC13	0x0
3536	chr21	17691360	17692529	+	LINC00478	0x0
3537	chr21	17923872	17925099	+	MIRLET7C	0x1
3538	chr21	18939729	18940861	+	CXADR	0x0
3539	chr21	18965434	18966673	−	BTG3	0x0
3540	chr21	19808934	19810061	−	TMPRSS15	0x0
3541	chr21	20716989	20718110	+	CHODL	0x0
3542	chr21	27096387	27097500	−	ATP5J	0x0
3543	chr21	27253244	27254417	−	APP	0x0
3544	chr21	27422807	27423993	−	APP	0x0
3545	chr21	27483816	27484951	−	APP	0x0
3546	chr21	27542144	27543260	−	APP	0x0
3547	chr21	28127783	28128979	+	MIR4759	0x0
3548	chr21	28208989	28210463	−	ADAMTS1	0x2
3549	chr21	28216087	28217212	−	ADAMTS1	0x2
3550	chr21	28337808	28339033	−	ADAMTS5	0x0
3551	chr21	30425923	30427216	+	USP16	0x2
3552	chr21	30698361	30699558	+	BACH1	0x0
3553	chr21	31014916	31016114	+	GRIK1-AS2	0x0
3554	chr21	32638350	32639765	−	TIAM1	0x2
3555	chr21	33036141	33037340	+	SOD1	0x0
3556	chr21	33040334	33041539	+	SOD1	0x0
3557	chr21	33089295	33090522	−	SCAF4	0x0
3558	chr21	33748942	33750183	−	SNORA80	0x0
3559	chr21	33984133	33985269	−	C21orf59	0x0
3560	chr21	34719386	34720535	+	IFNAR1	0x0
3561	chr21	35030387	35031585	+	ITSN1	0x0
3562	chr21	35127217	35128385	+	ITSN1	0x0
3563	chr21	35275722	35276821	−	ATP50	0x0
3564	chr21	35466827	35468201	+	SLC5A3	0x0
3565	chr21	36145165	36146372	+	LOC100506385	0x0
3566	chr21	37717977	37719131	+	MORC3	0x0
3567	chr21	37784041	37785217	+	CHAF1B	0x0
3568	chr21	37788598	37789672	+	CHAF1B	0x0
3569	chr21	38567541	38568686	+	TTC3	0x0
3570	chr21	38574002	38575432	+	TTC3	0x0
3571	chr21	38596923	38598132	−	DSCR3	0x0
3572	chr21	38632627	38633808	−	DSCR3	0x0
3573	chr21	40197423	40198595	+	ETS2	0x0
3574	chr21	40517282	40518471	−	PSMG1	0x0
3575	chr21	40718385	40719530	−	HMGN1	0x0
3576	chr21	42749811	42750988	+	MX2	0x2
3577	chr21	44268392	44269583	+	WDR4	0x0
3578	chr21	44479625	44480758	−	CBS	0x0
3579	chr21	44984500	44985920	+	RRP1B	0x0
3580	chr21	45090405	45091504	+	RRP1B	0x0
3581	chr21	45179520	45180696	+	PDXK	0x0
3582	chr21	45221421	45222618	+	RRP1	0x0
3583	chr21	45337879	45339028	+	AGPAT3	0x0
3584	chr21	45393639	45394947	+	AGPAT3	0x0
3585	chr21	45559550	45560770	+	C21orf33	0x0
3586	chr21	46188735	46189879	−	UBE2G2	0x2
3587	chr21	46225809	46226932	−	SUMO3	0x0
3588	chr21	46708339	46709547	+	LOC642852	0x0
3589	chr21	46893600	46894927	+	COL18A1	0x1
3590	chr21	46949302	46950441	−	SLC19A1	0x0
3591	chr21	46952281	46953369	−	SLC19A1	0x0
3592	chr21	46955505	46956592	−	SLC19A1	0x0
3593	chr21	47424319	47425504	+	COL6A1	0x0
3594	chr21	47547608	47548806	+	COL6A2	0x0
3595	chr21	47608898	47610162	−	LSS	0x0
3596	chr21	47738047	47739198	−	C21orf58	0x0
3597	chr22	18314151	18315281	−	MICAL3	0x0
3598	chr22	18571125	18572217	+	PEX26	0x0
3599	chr22	18954229	18955424	+	DGCR5	0x0
3600	chr22	19162785	19163956	−	SLC25A1	0x0
3601	chr22	19283535	19284762	+	MRPL40	0x0
3602	chr22	19362273	19363409	−	HIRA	0x0
3603	chr22	19822965	19824171	−	C22orf29	0x0
3604	chr22	19946011	19947236	+	COMT	0x0
3605	chr22	19949534	19950733	+	COMT	0x0
3606	chr22	19967218	19968536	−	ARVCF	0x0
3607	chr22	20842383	20843522	−	KLHL22	0x0
3608	chr22	21287555	21289058	+	CRKL	0x0
3609	chr22	21306986	21308085	+	CRKL	0x0
3610	chr22	21742936	21744308	+	RIMBP3B	0x0
3611	chr22	21742936	21744308	+	RIMBP3C	0x0
3612	chr22	22210386	22211557	−	MAPK1	0x0
3613	chr22	22672503	22673700	+	LOC96610	0x0
3614	chr22	23522226	23523427	+	BCR	0x1
3615	chr22	23980518	23981697	−	GUSBP11	0x0
3616	chr22	24236041	24237608	+	MIF	0x0
3617	chr22	24438704	24439858	+	CABIN1	0x0
3618	chr22	24907612	24908737	+	UPB1	0x0
3619	chr22	24936646	24937830	−	C22orf13	0x0
3620	chr22	24967397	24968547	+	SNRPD3	0x0
3621	chr22	25529046	25530177	+	KIAA1671	0x0
3622	chr22	25776890	25778026	−	LRP5L	0x0
3623	chr22	26104005	26105227	+	ADRBK2	0x0
3624	chr22	27282576	27283773	−	CRYBB1	0x0
3625	chr22	28248228	28249383	−	PITPNB	0x0
3626	chr22	28629801	28630944	−	TTC28	0x0
3627	chr22	28763509	28764779	−	TTC28	0x0
3628	chr22	28814029	28815169	−	TTC28	0x0
3629	chr22	28852585	28853737	−	TTC28	0x0
3630	chr22	28888395	28889599	−	TTC28	0x0
3631	chr22	29356334	29357530	+	ZNRF3	0x0
3632	chr22	29538797	29539902	+	KREMEN1	0x2
3633	chr22	29541059	29542208	+	KREMEN1	0x2
3634	chr22	29725923	29727091	−	AP1B1	0x0
3635	chr22	29727713	29730500	−	AP1B1	0x0
3636	chr22	29727713	29730500	−	MIR3653	0x0
3637	chr22	29727713	29730500	−	SNORD125	0x0
3638	chr22	31371430	31372477	+	TUG1	0x0
3639	chr22	31556509	31557707	+	RNF18S	0x0
3640	chr22	32226093	32227273	−	DEPDC5	0x0
3641	chr22	32894134	32895276	+	FBXO7	0x0
3642	chr22	33777348	33778521	−	LARGE	0x0
3643	chr22	34297389	34298523	−	LARGE	0x0
3644	chr22	34315651	34316828	−	LARGE	0x0
3645	chr22	35681160	35682395	+	HMGXB4	0x0
3646	chr22	35690280	35691464	+	HMGXB4	0x0
3647	chr22	35839585	35840776	+	MCM5	0x0
3648	chr22	36137244	36138456	−	RBFOX2	0x0
3649	chr22	36138942	36140500	−	RBFOX2	0x0
3650	chr22	36214874	36216032	−	RBFOX2	0x0
3651	chr22	36395321	36396462	−	RBFOX2	0x0
3652	chr22	36677011	36678199	−	MYH9	0x2
3653	chr22	36680665	36681891	−	MYH9	0x2
3654	chr22	36704808	36705986	−	MYH9	0x2
3655	chr22	37803544	37804731	−	ELFN2	0x0
3656	chr22	38007253	38008489	+	GGA1	0x2
3657	chr22	38200770	38201857	+	H1F0	0x0
3658	chr22	38313130	38314351	+	MICALL1	0x0
3659	chr22	38616456	38617636	−	TMEM184B	0x0
3660	chr22	38690099	38691306	−	CSNK1E	0x0
3661	chr22	38691643	38692846	−	CSNK1E	0x0
3662	chr22	38851091	38852298	+	KDELR3	0x0
3663	chr22	38879086	38881782	−	DDX17	0x0
3664	chr22	38896636	38897754	−	DDX17	0x0
3665	chr22	39079245	39080420	+	TOMM22	0x0
3666	chr22	39126436	39127627	+	GTPBP1	0x0
3667	chr22	39258060	39259789	−	CBX6	0x0
3668	chr22	39709252	39710490	−	RP13	0x0
3669	chr22	39709252	39710490	−	SNORD83B	0x0
3670	chr22	39710669	39711896	−	RPL3	0x0
3671	chr22	39710669	39711896	−	SNORD83A	0x0
3672	chr22	39713023	39714106	−	RPL3	0x0
3673	chr22	39714525	39715679	−	RPL3	0x0
3674	chr22	39714525	39715679	−	SNORD43	0x0
3675	chr22	39824331	39825448	+	TAB1	0x0
3676	chr22	40603841	40604999	+	TNRC6B	0x0
3677	chr22	41032643	41033828	+	MCHR1	0x2
3678	chr22	41322022	41323150	+	XPNPEP3	0x0
3679	chr22	41348974	41350206	+	RBX1	0x1
3680	chr22	41367993	41369234	+	RBX1	0x1
3681	chr22	41650943	41652115	−	RANGAP1	0x0
3682	chr22	41672402	41673555	−	RANGAP1	0x0
3683	chr22	41830391	41831584	−	TOB2	0x0
3684	chr22	41921316	41922493	−	POLR3H	0x0
3685	chr22	41931206	41932394	−	POLR3H	0x0
3686	chr22	41989044	41990224	−	PMM1	0x0
3687	chr22	42017457	42018631	+	XRCC6	0x0
3688	chr22	42031586	42032802	+	XRCC6	0x0
3689	chr22	42070194	42071398	−	NHP2L1	0x0
3690	chr22	42205327	42206535	+	CCDC134	0x0
3691	chr22	42224006	42225166	+	CCDC134	0x0
3692	chr22	42228697	42229797	+	SREBF2	0x0
3693	chr22	42244116	42245325	+	SREBF2	0x0
3694	chr22	42301585	42303689	+	SREBF2	0x0
3695	chr22	42390611	42391960	+	SEPTS	0x0
3696	chr22	42605304	42606458	−	TCF20	0x0
3697	chr22	42911537	42912665	−	RRP7A	0x0
3698	chr22	42960739	42961876	−	RRP7B	0x0
3699	chr22	43010681	43011963	+	RNU12	0x0
3700	chr22	43014427	43015900	−	CYB5R3	0x0
3701	chr22	44403105	44404301	+	PARVB	0x0
3702	chr22	45364086	45365225	−	PHF21B	0x0
3703	chr22	45568661	45569815	+	NUP50	0x0
3704	chr22	45580847	45581958	+	NUP50	0x0
3705	chr22	45921134	45922335	+	FBLN1	0x0
3706	chr22	46088330	46089523	+	ATXN10	0x0
3707	chr22	46124715	46126044	+	ATXN10	0x0
3708	chr22	46134049	46135230	+	ATXN10	0x0
3709	chr22	46156733	46157865	+	MIR4762	0x0
3710	chr22	46268284	46269464	+	ATXN10	0x0
3711	chr22	46483698	46484878	+	MIRLET7BHG	0x0
3712	chr22	46494420	46495618	+	MIRLET7BHG	0x0
3713	chr22	46634509	46635753	+	PPARA	0x0
3714	chr22	46781824	46783035	−	CELSR1	0x0
3715	chr22	46946646	46947830	−	CELSR1	0x0
3716	chr22	47270127	47271321	+	TBC1D22A	0x0
3717	chr22	50205194	50206352	−	BRD1	0x0
3718	chr22	50210282	50211470	−	BRD1	0x0
3719	chr22	50713376	50714569	−	PLXNB2	0x0
3720	chr22	50719855	50721037	−	PLXNB2	0x0
3721	chr22	50831729	50832913	+	PPP6R2	0x0
3722	chr22	50904081	50906314	−	SBF1	0x0
3723	chr22	50970887	50972085	+	NCAPH2	0x0
3724	chr22	51063279	51064390	−	ARSA	0x0
3725	chr3	3186604	3187841	+	TRNT1	0x0
3726	chr3	8024180	8025374	−	LOC100288428	0x0
3727	chr3	8265114	8266333	+	LMCD1	0x0
3728	chr3	9431261	9432805	−	LOC440944	0x0
3729	chr3	9486201	9487428	+	SETD5	0x0
3730	chr3	9857220	9858434	+	TTLL3	0x0
3731	chr3	10167287	10168486	+	BRK1	0x0
3732	chr3	10321861	10323056	+	TATDN2	0x0
3733	chr3	11401512	11402751	+	ATG7	0x0
3734	chr3	11597538	11598649	−	VGLL4	0x0
3735	chr3	12064814	12066017	+	SYN2	0x2
3736	chr3	12147964	12149112	+	SYN2	0x2
3737	chr3	12560059	12561224	+	TSEN2	0x0
3738	chr3	12625214	12626361	−	RAF1	0x2
3739	chr3	12844503	12845700	+	CAND2	0x0
3740	chr3	12881152	12882451	−	RPL32	0x0
3741	chr3	12881152	12882451	−	SNORA7A	0x0
3742	chr3	12982633	12983771	−	IQSEC1	0x0
3743	chr3	13035839	13037016	−	IQSEC1	0x0
3744	chr3	13280722	13281919	−	NUP210	0x2
3745	chr3	13313379	13314536	−	NUP210	0x2
3746	chr3	13357743	13359380	−	NUP210	0x2
3747	chr3	13783339	13784537	+	LOC285375	0x0
3748	chr3	14199493	14200692	−	XPC	0x2
3749	chr3	15483124	15484230	+	EAF1	0x0
3750	chr3	15779482	15780795	+	BTD	0x0
3751	chr3	15885578	15886855	−	ANKRD28	0x0
3752	chr3	16275601	16276775	+	GALNTL2	0x0
3753	chr3	16459402	16460560	−	RFTN1	0x0
3754	chr3	17052965	17054111	+	PICL2	0x0
3755	chr3	20025601	20026775	+	RAB5A	0x0
3756	chr3	23383956	23385109	+	MIR548AC	0x0
3757	chr3	23436605	23437832	+	MIR548AC	0x0
3758	chr3	23925735	23926895	+	UBE2E1	0x0
3759	chr3	23932123	23933247	+	UBE2E1	0x0
3760	chr3	23960126	23962663	+	RPL15	0x0
3761	chr3	23995512	23996762	+	NR1D2	0x0
3762	chr3	25639039	25640283	−	TOP2B	0x0
3763	chr3	29587021	29588218	+	RBMS3	0x0
3764	chr3	31269659	31270890	+	STT3B	0x0
3765	chr3	31620850	31622065	+	STT3B	0x0
3766	chr3	31699275	31700456	+	STT3B	0x0
3767	chr3	31945766	31946935	+	OSBPL10	0x0
3768	chr3	32078480	32079674	+	ZNF860	0x0
3769	chr3	32411082	32412230	+	CMTM8	0x0
3770	chr3	32599973	32601163	−	DYNC1LI1	0x0
3771	chr3	32609995	32611224	−	DYNC1LI1	0x0
3772	chr3	32938215	32939410	+	TRIM71	0x0
3773	chr3	33128714	33129913	−	TMPPE	0x0
3774	chr3	33173472	33174713	+	CRTAP	0x0
3775	chr3	33643362	33644461	−	CLASP2	0x0
3776	chr3	33873618	33874717	+	PDCD6IP	0x0
3777	chr3	36726163	36727403	+	STAC	0x0
3778	chr3	37080825	37081931	+	MLH1	0x1
3779	chr3	37189849	37191014	−	LRRFIP2	0x0
3780	chr3	37465287	37466386	+	C3orf35	0x0
3781	chr3	38427202	38428303	+	XYLB	0x0
3782	chr3	38668691	38669899	−	SCN5A	0x2
3783	chr3	39449312	39450619	+	RPSA	0x0
3784	chr3	39449312	39450619	+	SNORA6	0x0
3785	chr3	39452000	39454062	+	RPSA	0x0
3786	chr3	39452000	39454062	+	SNORA62	0x0
3787	chr3	40352965	40354173	+	EIF1B	0x0
3788	chr3	40504882	40506079	+	RPL14	0x0
3789	chr3	40522637	40523826	+	ZNF619	0x0
3790	chr3	40713594	40714769	+	ZNF621	0x0
3791	chr3	41268246	41269401	+	CTNNB1	0x2
3792	chr3	41280979	41282170	+	CTNNB1	0x2
3793	chr3	42172215	42173420	+	TRAK1	0x0
3794	chr3	42262814	42263984	+	TRAK1	0x0
3795	chr3	42627709	42628944	+	SS18L2	0x0
3796	chr3	42661569	42662722	+	NKTR	0x0
3797	chr3	42825272	42826470	−	HIGD1A	0x0
3798	chr3	43369372	43370583	+	SNRK	0x0
3799	chr3	43513438	43514642	+	SNRK	0x0
3800	chr3	43735287	43736484	+	ABHD5	0x0
3801	chr3	44534839	44536016	−	ZNF445	0x0
3802	chr3	44672062	44673163	+	ZNF197	0x0
3803	chr3	44879232	44880427	+	KIF15	0x0
3804	chr3	45532675	45533841	+	LARS2	0x0
3805	chr3	45696671	45697833	+	LIMD1	0x1
3806	chr3	45729920	45731109	−	LOC644714	0x0
3807	chr3	47030877	47031967	+	NBEAL2	0x0
3808	chr3	47050355	47051532	+	NBEAL2	0x0
3809	chr3	47450648	47451750	+	PTPN23	0x0
3810	chr3	47466455	47467633	−	SCAP	0x0
3811	chr3	47469475	47470674	−	SCAP	0x0
3812	chr3	47529404	47530562	−	C3orf75	0x0
3813	chr3	47603307	47604405	−	CSPG5	0x0
3814	chr3	47627164	47629184	−	SMARCC1	0x0
3815	chr3	47703473	47704650	−	SMARCC1	0x0
3816	chr3	47719118	47720319	−	SMARCC1	0x0
3817	chr3	47892891	47895011	−	MAP4	0x0
3818	chr3	47932060	47933280	−	MAP4	0x0
3819	chr3	47985416	47986611	−	MAP4	0x0
3820	chr3	48313866	48315070	+	ZNF589	0x0
3821	chr3	48455708	48456825	−	PLXNB1	0x0
3822	chr3	48460349	48461527	−	PLXNB1	0x0
3823	chr3	48730604	48732071	−	IP6K2	0x0
3824	chr3	48784557	48786041	−	PRKAR2A	0x0
3825	chr3	48978026	48979203	+	ARIH2	0x0
3826	chr3	49049998	49051180	+	WDR6	0x0
3827	chr3	49059757	49060931	+	NDUFAF3	0x0
3828	chr3	49298828	49299995	−	C3orf62	0x0
3829	chr3	49306933	49308097	+	MIR4271	0x0
3830	chr3	49396629	49397880	−	RHOA	0x1
3831	chr3	49462515	49463654	−	NICN1	0x0
3832	chr3	49515374	49516569	+	DAG1	0x0
3833	chr3	49570399	49571592	+	DAG1	0x0
3834	chr3	49736551	49737732	+	RNF123	0x0
3835	chr3	50263689	50264867	+	SLC38A3	0x2
3836	chr3	50773542	50774742	+	DOCK3	0x0
3837	chr3	51042193	51043377	+	DOCK3	0x0
3838	chr3	51242911	51244156	+	DOCK3	0x0
3839	chr3	51347120	51348316	+	DOCK3	0x0
3840	chr3	51572431	51573592	+	RAD54L2	0x0
3841	chr3	51697732	51698844	+	RAD54L2	0x0
3842	chr3	51727913	51729115	−	IQCF6	0x0
3843	chr3	52002235	52003383	−	ABHD14B	0x0
3844	chr3	52027879	52028994	−	RPL29	0x0
3845	chr3	52561632	52562808	−	NT5DC2	0x0
3846	chr3	52569766	52570959	+	C3orf78	0x0
3847	chr3	52635477	52636633	−	PBRM1	0x1
3848	chr3	52713144	52714273	−	PBRM1	0x1
3849	chr3	52728009	52729194	−	GLT8D1	0x0
3850	chr3	53260228	53261442	−	TKT	0x0
3851	chr3	53327386	53328534	−	DCP1A	0x0
3852	chr3	53893275	53894463	−	ACTR8	0x0
3853	chr3	56105579	56106778	+	CCDC66	0x0
3854	chr3	56253146	56254314	−	ERC2	0x0
3855	chr3	56657136	56658267	−	FAM208A	0x0
3856	chr3	56692410	56693565	+	CCDC66	0x0
3857	chr3	56712433	56713636	−	FAM208A	0x0
3858	chr3	58066827	58068032	+	FLNB	0x2
3859	chr3	59526653	59527853	−	FHIT	0x1
3860	chr3	59803894	59805090	−	FHIT	0x1
3861	chr3	60392540	60393686	−	FHIT	0x1
3862	chr3	60740685	60741849	−	FHIT	0x1
3863	chr3	61079221	61080390	−	FHIT	0x1
3864	chr3	61684302	61685482	−	ID2B	0x0
3865	chr3	61728103	61729326	−	ID2B	0x0
3866	chr3	61781350	61782617	+	PTPRG	0x0
3867	chr3	61821361	61822559	+	PTPRG	0x0
3868	chr3	62252507	62253654	+	PTPRG	0x0
3869	chr3	63530565	63531774	+	SYNPR	0x0
3870	chr3	63898015	63899478	+	ATXN7	0x0
3871	chr3	64081176	64082354	−	PRICKLE2	0x0
3872	chr3	65581623	65582779	−	MAGI1	0x0
3873	chr3	69061262	69062419	−	C3orf64	0x0
3874	chr3	69109074	69110269	−	UBA3	0x0
3875	chr3	69383812	69385009	−	FRMD4B	0x0
3876	chr3	69937863	69939029	+	MITF	0x2
3877	chr3	71049846	71051051	−	FOXP1	0x1
3878	chr3	71310174	71311273	−	FOXP1	0x1
3879	chr3	71803897	71805392	+	GPR27	0x0
3880	chr3	72440865	72442047	−	RYBP	0x0
3881	chr3	73159615	73160858	+	PPP4R2	0x0
3882	chr3	75467516	75468695	−	FAM86DP	0x0
3883	chr3	75778673	75780352	−	ZNF717	0x0
3884	chr3	76067180	76068297	+	MIR4273	0x0
3885	chr3	76116679	76117859	+	MIR4273	0x0
3886	chr3	77588421	77589624	−	ROBO1	0x2
3887	chr3	78210509	78211683	+	ROBO2	0x2
3888	chr3	78725364	78726526	−	ROBO1	0x2
3889	chr3	78776220	78777399	−	ROBO1	0x2
3890	chr3	78965685	78966835	−	ROBO1	0x2
3891	chr3	79746721	79747916	+	ROBO2	0x2
3892	chr3	87302575	87303778	+	CHMP2B	0x2
3893	chr3	88188033	88189234	+	ZNF654	0x0
3894	chr3	93845492	93846677	+	NSUN3	0x0
3895	chr3	96070305	96071474	+	EPHA6	0x0
3896	chr3	96336252	96337451	−	MINA	0x0
3897	chr3	96706235	96707403	+	EPHA6	0x0
3898	chr3	98298899	98300073	−	CPOX	0x0
3899	chr3	98514482	98515659	−	DCBLD2	0x0
3900	chr3	99674284	99675721	+	C3orf26	0x0
3901	chr3	100083078	100084175	−	TOMM70A	0x0
3902	chr3	101294947	101296226	−	SENP7	0x0
3903	chr3	101311953	101313173	+	PCNP	0x0
3904	chr3	101427409	101428630	+	LOC285359	0x0
3905	chr3	101523677	101524892	−	FAM55C	0x0
3906	chr3	105577927	105579124	−	CBLB	0x2
3907	chr3	112728872	112730023	−	C3orf17	0x0
3908	chr3	112731024	112732187	−	C3orf17	0x0
3909	chr3	113351035	113352266	+	SIDT1	0x0
3910	chr3	113409806	113410988	−	KIAA2018	0x0
3911	chr3	113437715	113438865	−	NAA50	0x0
3912	chr3	113439795	113440972	−	NAA50	0x0
3913	chr3	113528980	113530968	+	ATP6V1A	0x0
3914	chr3	113782739	113783838	+	QTRTD1	0x0
3915	chr3	114068620	114069796	−	ZBTB20	0x0
3916	chr3	119247667	119248873	+	TIMMDC1	0x0
3917	chr3	119509622	119510841	+	NR1I2	0x0
3918	chr3	119812267	119813380	−	GSK3B	0x2
3919	chr3	120434017	120435211	−	RABL3	0x0
3920	chr3	120955706	120956915	−	POLQ	0x0
3921	chr3	122841602	122842804	+	PDIA5	0x0
3922	chr3	124988538	124989715	−	ZNF148	0x0
3923	chr3	125165792	125166986	−	SNX4	0x2
3924	chr3	125797486	125798706	−	SLC41A3	0x0
3925	chr3	125833502	125834789	−	ALDH1L1	0x4
3926	chr3	126180019	126181440	−	ZXDC	0x0
3927	chr3	126183659	126184858	−	ZXDC	0x0
3928	chr3	126322569	126323774	−	TXNRD3	0x0
3929	chr3	126707552	126708763	+	PLXNA1	0x0
3930	chr3	127380537	127381652	+	PODXL2	0x0
3931	chr3	127788558	127790058	+	SEC61A1	0x0
3932	chr3	127793410	127794585	−	RUVBL1	0x2
3933	chr3	128198861	128200036	−	GATA2	0x2
3934	chr3	128207961	128209161	+	DNAJB8-AS1	0x0
3935	chr3	128338243	128339419	−	RPN1	0x2
3936	chr3	128451591	128452997	+	RAB7A	0x0
3937	chr3	128531822	128533064	+	RAB7A	0x0
3938	chr3	128953745	128954950	+	COPG1	0x0
3939	chr3	129273522	129274695	−	PLXND1	0x0
3940	chr3	129296466	129297816	−	PLXND1	0x0
3941	chr3	129309709	129310948	+	H1FOO	0x2
3942	chr3	130462865	130464003	−	P1K3R4	0x0
3943	chr3	131197366	131198647	−	SNORA58	0x0
3944	chr3	131947407	131948608	−	CPNE4	0x0
3945	chr3	132293236	132294410	−	ACAD11	0x0
3946	chr3	132293236	132294410	−	NPHP3-ACAD11	0x0
3947	chr3	132394900	132396036	+	UBA5	0x0
3948	chr3	132809501	132810699	+	TMEM108	0x0
3949	chr3	133361690	133362902	−	TOPBP1	0x0
3950	chr3	133875654	133876850	−	RYK	0x0
3951	chr3	134501746	134502960	−	KY	0x0
3952	chr3	134713228	134714454	+	EPHB1	0x2
3953	chr3	136676705	136677925	+	IL20RB	0x0
3954	chr3	141324383	141325571	+	RASA2	0x0
3955	chr3	141644100	141645202	+	ATP1B3	0x0
3956	chr3	142047179	142048291	−	XRN1	0x1
3957	chr3	142391861	142393182	+	PLS1	0x0
3958	chr3	142774866	142776027	+	U2SURP	0x0
3959	chr3	143553099	143554255	−	SLC9A9	0x0
3960	chr3	148748280	148749431	−	HLTF	0x1
3961	chr3	148757934	148759261	−	HLTF	0x1
3962	chr3	149672385	149673561	−	PFN2	0x0
3963	chr3	149682334	149684418	−	PFN2	0x0
3964	chr3	149685647	149686790	−	PFN2	0x0
3965	chr3	149699572	149700765	−	PFN2	0x0
3966	chr3	150261659	150262838	−	SERP1	0x0
3967	chr3	150381802	150383036	+	SELT	0x0
3968	chr3	150905323	150906552	+	MED12L	0x2
3969	chr3	152019844	152021041	+	MBNL1	0x0
3970	chr3	152525159	152526317	−	TMEM14E	0x0
3971	chr3	154006950	154008133	−	DHX36	0x0
3972	chr3	154017847	154018991	−	DHX36	0x0
3973	chr3	155610832	155611932	+	GMPS	0x2
3974	chr3	156258040	156259216	−	SSR3	0x0
3975	chr3	156259638	156260819	−	SSR3	0x0
3976	chr3	159505029	159506215	+	IQCJ-SCHIP1	0x0
3977	chr3	159505029	159506215	+	SCHIPl	0x0
3978	chr3	160101112	160102239	−	IFT80	0x0
3979	chr3	160135040	160136208	+	SMC4	0x0
3980	chr3	160145967	160147164	+	SMC4	0x0
3981	chr3	160151049	160152148	+	SMC4	0x0
3982	chr3	160232247	160233581	−	KPNA4	0x0
3983	chr3	160232247	160233581	−	SCARNA7	0x0
3984	chr3	161146335	161147562	−	SPTSSB	0x0
3985	chr3	162751663	162752835	+	OTOL1	0x0
3986	chr3	167812547	167813770	−	GOLIM4	0x0
3987	chr3	168916004	168917153	−	MECOM	0x0
3988	chr3	169016868	169018187	−	MECOM	0x0
3989	chr3	169248357	169249556	−	MECOM	0x0
3990	chr3	169257396	169258572	−	MECOM	0x0
3991	chr3	169276218	169277388	−	MECOM	0x0
3992	chr3	169300966	169302116	−	MECOM	0x0
3993	chr3	169321337	169322504	−	MECOM	0x0
3994	chr3	169481843	169483395	−	TERC	0x0
3995	chr3	169489439	169490639	+	MYNN	0x0
3996	chr3	169712126	169713251	+	SEC62	0x0
3997	chr3	169811003	169812221	−	PHC3	0x0
3998	chr3	170113003	170114159	+	SKIL	0x0
3999	chr3	173662250	173663437	+	NLGN1	0x2
4000	chr3	174095052	174096268	+	NLGN1	0x2
4001	chr3	174689747	174690921	−	SPATA16	0x0
4002	chr3	175180913	175182083	+	NAALADL2	0x0
4003	chr3	176738627	176739772	−	TBL1XR1	0x2
4004	chr3	178724112	178725336	−	ZMAT3	0x0
4005	chr3	178897509	178898703	+	PIK3CA	0x2
4006	chr3	179040437	179041633	+	ZNF639	0x2
4007	chr3	179089083	179090273	+	MFN1	0x0
4008	chr3	179113461	179114610	−	GNB4	0x2
4009	chr3	179117003	179118152	−	GNB4	0x2
4010	chr3	179305509	179306667	+	ACTL6A	0x0
4011	chr3	179879102	179880325	−	PEX5L	0x0
4012	chr3	180631103	180632281	−	DNAJC19	0x0
4013	chr3	181540082	181541351	−	FU46066	0x0
4014	chr3	182582782	182583964	+	ATP11B	0x0
4015	chr3	182750101	182751276	−	MCCC1	0x0
4016	chr3	183169134	183170340	+	LOC100505687	0x0
4017	chr3	183353570	183354694	+	KLHL24	0x0
4018	chr3	183398003	183399122	+	KLHL24	0x0
4019	chr3	183580621	183581759	−	PARL	0x0
4020	chr3	183744592	183745798	−	ABCC5	0x0
4021	chr3	183854121	183855271	+	EIF2B5	0x0
4022	chr3	183867148	183868604	+	EIF2B5	0x0
4023	chr3	183890038	183891239	+	DVL3	0x0
4024	chr3	183900738	183902213	+	AP2M1	0x0
4025	chr3	184039630	184040778	+	EIF4G1	0x0
4026	chr3	184042919	184044133	+	EIF4G1	0x0
4027	chr3	184042919	184044133	+	SNORD66	0x0
4028	chr3	184051974	184053512	+	EIF4G1	0x0
4029	chr3	184084326	184085542	+	POLR2H	0x0
4030	chr3	184427867	184429119	−	MAGEF1	0x0
4031	chr3	184429133	184430288	−	MAGEF1	0x0
4032	chr3	184563055	184564277	+	VPS8	0x0
4033	chr3	185347678	185348961	+	SENP2	0x0
4034	chr3	185361867	185363192	−	IGF2BP2	0x0
4035	chr3	185439837	185441123	−	IGF2BP2	0x0
4036	chr3	185505712	185506895	−	IGF2BP2	0x0
4037	chr3	185634368	185635555	−	TRA2B	0x0
4038	chr3	185649515	185650644	−	TRA2B	0x0
4039	chr3	185653526	185654615	−	TRA2B	0x0
4040	chr3	186503929	186505190	+	EIF4A2	0x2
4041	chr3	186503929	186505190	+	MIR1248	0x0
4042	chr3	186503929	186505190	+	SNORA63	0x0
4043	chr3	186503929	186505190	+	SNORA81	0x0
4044	chr3	186507201	186508333	−	RFC4	0x0
4045	chr3	186617309	186618709	+	ST6GAL1	0x0
4046	chr3	186759892	186761084	+	ST6GAL1	0x0
4047	chr3	187388143	187389326	+	LOC100131635	0x0
4048	chr3	192515576	192516752	−	MB21D2	0x0
4049	chr3	193855605	193856801	+	HES1	0x4
4050	chr3	194125256	194126390	−	ATP13A3	0x0
4051	chr3	194171170	194172310	−	ATP13A3	0x0
4052	chr3	194386411	194387704	−	LSG1	0x0
4053	chr3	195776095	195777234	−	TFRC	0x2
4054	chr3	195962385	195963505	−	PCYT1A	0x0
4055	chr3	196074014	196075163	−	UBXN7	0x0
4056	chr3	196081421	196082538	−	UBXN7	0x0
4057	chr3	196118165	196119364	−	UBXN7	0x0
4058	chr3	196119861	196121051	−	UBXN7	0x0
4059	chr3	196511321	196512475	−	CEP19	0x0
4060	chr3	196728214	196729390	−	MFI2	0x0
4061	chr3	196842301	196843472	−	DLG1	0x1
4062	chr3	197281533	197282691	+	FYTTD1	0x0
4063	chr3	197679722	197680920	+	RPL35A	0x0
4064	chr3	197682245	197683345	+	RPL35A	0x0
4065	chr4	1209320	1210535	−	CTBP1	0x1
4066	chr4	1218742	1219931	−	CTBP1	0x1
4067	chr4	1231531	1232630	−	CTBP1	0x1
4068	chr4	1234606	1235835	−	CTBP1	0x1
4069	chr4	1342835	1343966	+	KIAA1530	0x4
4070	chr4	1672052	1673244	−	FAM53A	0x0
4071	chr4	1694014	1695533	−	SLBP	0x0
4072	chr4	1713372	1714566	−	SLBP	0x0
4073	chr4	1726499	1727631	+	TACC3	0x0
4074	chr4	1738532	1739923	+	TACC3	0x0
4075	chr4	1746121	1747254	+	TACC3	0x0
4076	chr4	1805357	1806534	+	FGFR3	0x2
4077	chr4	1813767	1815003	−	LETM1	0x2
4078	chr4	1824830	1826025	−	LETM1	0x2
4079	chr4	1918109	1919304	+	WHSC1	0x2
4080	chr4	1936420	1937586	+	WHSC1	0x2
4081	chr4	1957214	1958422	+	WHSC1	0x2
4082	chr4	1975823	1977043	+	SCARNA22	0x0
4083	chr4	1975823	1977043	+	WHSC1	0x2
4084	chr4	1981796	1982993	+	WHSC1	0x2
4085	chr4	2067921	2069165	+	NAT8L	0x0
4086	chr4	2077034	2078212	−	POLN	0x0
4087	chr4	2248957	2250057	−	MXD4	0x0
4088	chr4	2581395	2582619	+	FAM193A	0x0
4089	chr4	2827638	2829176	+	SH3BP2	0x0
4090	chr4	2906074	2907292	+	ADD1	0x0
4091	chr4	2940758	2941861	−	NOP14	0x0
4092	chr4	3252082	3253256	−	HTT-AS1	0x0
4093	chr4	4683894	4685085	+	LOC100507266	0x0
4094	chr4	5818067	5819249	+	EVC	0x0
4095	chr4	6200362	6201539	−	JAKMIP1	0x0
4096	chr4	6642990	6644560	+	MRFAP1	0x0
4097	chr4	6709345	6710474	−	MRFAP1L1	0x0
4098	chr4	6998419	6999606	+	TBC1D14	0x0
4099	chr4	7033051	7034321	+	TBC1D14	0x0
4100	chr4	7583649	7584931	+	SORCS2	0x0
4101	chr4	8459163	8460338	+	METTL19	0x0
4102	chr4	11684050	11685227	−	HS3ST1	0x0
4103	chr4	13426350	13427562	−	RAB28	0x0
4104	chr4	13731061	13732284	+	LOC152742	0x0
4105	chr4	17625172	17626370	+	MED28	0x0
4106	chr4	17819468	17820625	+	NCAPG	0x0
4107	chr4	17838682	17839842	+	NCAPG	0x0
4108	chr4	17841200	17842430	+	NCAPG	0x0
4109	chr4	18013434	18014610	−	LCORL	0x0
4110	chr4	18576184	18577360	−	LCORL	0x0
4111	chr4	20253069	20255107	+	SLIT2	0x1
4112	chr4	20357968	20359022	+	SLIT2-IT1	0x0
4113	chr4	20377297	20378395	+	SLIT2-IT1	0x0
4114	chr4	20414007	20415155	+	SLIT2-IT1	0x0
4115	chr4	20420764	20421861	+	SLIT2-IT1	0x0
4116	chr4	20526965	20528169	+	SLIT2	0x1
4117	chr4	20554935	20556122	+	SLIT2	0x1
4118	chr4	20590724	20591907	+	SLIT2	0x1
4119	chr4	20621379	20622480	+	SLIT2	0x1
4120	chr4	25251620	25252796	+	PI4K2B	0x0
4121	chr4	25278154	25279346	+	PI4K2B	0x0
4122	chr4	25748638	25749824	−	SEL1L3	0x0
4123	chr4	26416536	26417741	+	RBPJ	0x0
4124	chr4	27023705	27024866	+	STIM2	0x0
4125	chr4	30525911	30527106	−	CCKAR	0x2
4126	chr4	30724060	30725257	+	PCDH7	0x2
4127	chr4	30732429	30733530	+	PCDH7	0x2
4128	chr4	30737453	30738629	+	PCDH7	0x2
4129	chr4	30755239	30756386	+	PCDH7	0x2
4130	chr4	37437853	37439050	−	RELL1	0x0
4131	chr4	37634961	37637224	−	RELL1	0x0
4132	chr4	38618668	38619867	+	KLF3	0x0
4133	chr4	39114266	39115366	+	KLHL5	0x0
4134	chr4	39276035	39277181	+	WDR19	0x0
4135	chr4	39286725	39287909	+	WDR19	0x0
4136	chr4	39708907	39710122	+	UBE2K	0x0
4137	chr4	39782183	39783294	+	UBE2K	0x0
4138	chr4	39978528	39979627	−	PDS5A	0x0
4139	chr4	40601188	40602333	−	RBM47	0x0
4140	chr4	41259046	41260283	+	UCHL1	0x1
4141	chr4	41264120	41265319	+	UCHL1	0x1
4142	chr4	41269710	41270980	+	UCHL1	0x1
4143	chr4	42088879	42090056	+	SLC30A9	0x0
4144	chr4	42202449	42203618	+	SLC30A9	0x0
4145	chr4	43411605	43412801	−	ATP8A1	0x0
4146	chr4	46893136	46894294	−	COX7B2	0x0
4147	chr4	47708099	47709348	+	ATP10D	0x0
4148	chr4	47882394	47883542	−	NFXL1	0x0
4149	chr4	48413731	48414890	+	SLAIN2	0x0
4150	chr4	48438539	48439739	+	SLAIN2	0x0
4151	chr4	48862472	48863658	+	OCIAD1	0x0
4152	chr4	52734129	52735328	+	DCUN1D4	0x0
4153	chr4	53461921	53463125	−	USP46	0x0
4154	chr4	54283388	54284590	+	FIP1L1	0x2
4155	chr4	54953571	54954744	+	GSX2	0x0
4156	chr4	55841774	55842881	−	KDR	0x2
4157	chr4	56280443	56281494	+	TMEM165	0x0
4158	chr4	56962978	56964223	+	CEP135	0x0
4159	chr4	57325750	57327992	+	PAICS	0x0
4160	chr4	58383343	58384447	+	LOC255130	0x0
4161	chr4	59221215	59222390	−	IGFBP7	0x1
4162	chr4	62093328	62094523	+	LPHN3	0x2
4163	chr4	62551899	62553121	+	LPHN3	0x2
4164	chr4	62774206	62775380	+	LPHN3	0x2
4165	chr4	66438864	66440463	+	LOC100144602	0x0
4166	chr4	68294835	68295976	−	CENPC1	0x0
4167	chr4	68321540	68322718	−	CENPC1	0x0
4168	chr4	69097071	69098228	−	TMPRSS11B	0x0
4169	chr4	70296091	70297349	−	UGT2B4	0x0
4170	chr4	71553746	71554940	+	UTP3	0x0
4171	chr4	73941209	73942338	−	ANKRD17	0x0
4172	chr4	73955544	73957661	−	ANKRD17	0x0
4173	chr4	73986039	73987204	−	ANKRD17	0x0
4174	chr4	74079369	74080510	−	ANKRD17	0x0
4175	chr4	74102690	74103817	−	ANKRD17	0x0
4176	chr4	74109735	74110834	−	ANKRD17	0x0
4177	chr4	76569124	76570342	−	G3BP2	0x0
4178	chr4	76648143	76649358	−	G3BP2	0x0
4179	chr4	76660425	76661657	+	USO1	0x0
4180	chr4	76733874	76735088	+	USO1	0x0
4181	chr4	76806599	76808121	+	USO1	0x0
4182	chr4	77265081	77266329	+	FAM47E-STBD1	0x0
4183	chr4	77265081	77266329	+	STBD1	0x0
4184	chr4	77372618	77373794	+	SHROOM3	0x2
4185	chr4	77766703	77767861	−	SOWAHB	0x0
4186	chr4	77768802	77770022	+	SHROOM3	0x2
4187	chr4	77958275	77959447	+	SEPT11	0x0
4188	chr4	77967833	77969064	−	CCNI	0x0
4189	chr4	77969179	77970319	−	CCNI	0x0
4190	chr4	77976650	77978723	−	CCNI	0x0
4191	chr4	79053658	79054798	−	CNOT6L	0x0
4192	chr4	79175849	79177015	+	FRAS1	0x0
4193	chr4	79205034	79206238	+	FRAS1	0x0
4194	chr4	79410767	79411878	+	FRAS1	0x0
4195	chr4	79438573	79439806	+	FRAS1	0x0
4196	chr4	79734146	79735341	+	BMP2K	0x0
4197	chr4	79840005	79841132	−	PAQR3	0x0
4198	chr4	80274113	80275302	−	NAA11	0x0
4199	chr4	83268298	83269488	−	HNRNPD	0x0
4200	chr4	83274558	83275765	−	HNRNPD	0x0
4201	chr4	83280150	83281278	−	HNRNPD	0x0
4202	chr4	83343963	83345140	−	HNRPDL	0x0
4203	chr4	83347069	83348169	−	HNRPDL	0x0
4204	chr4	83550678	83551963	−	SCD5	0x0
4205	chr4	83818751	83819908	−	LOC100499177	0x0
4206	chr4	86021366	86022519	+	WDFY3-AS2	0x0
4207	chr4	87393257	87394403	−	MAPK10	0x0
4208	chr4	87515041	87516221	+	PTPN13	0x0
4209	chr4	87653247	87654357	+	PTPN13	0x0
4210	chr4	87870545	87871718	−	LOC100506746	0x0
4211	chr4	87940038	87941259	+	AFF1	0x0
4212	chr4	88099083	88100238	−	KLHL8	0x0
4213	chr4	88137806	88138917	−	KLHL8	0x0
4214	chr4	89777339	89778499	−	FAM13A	0x2
4215	chr4	89954916	89956116	−	FAM13A	0x2
4216	chr4	90663937	90665134	+	LOC644248	0x0
4217	chr4	93531591	93532768	+	GRID2	0x0
4218	chr4	95416050	95417252	+	PDLIM5	0x0
4219	chr4	95575127	95576327	+	PDLIM5	0x0
4220	chr4	96396095	96397271	−	UNC5C	0x1
4221	chr4	99563213	99564313	−	TSPAN5	0x0
4222	chr4	99850331	99851505	+	METAP1	0x0
4223	chr4	100868849	100870090	−	H2AFZ	0x0
4224	chr4	103717651	103719025	−	UBE2D3	0x0
4225	chr4	104725398	104726574	−	TACR3	0x0
4226	chr4	106026648	106027830	+	TET2	0x1
4227	chr4	106057841	106059021	−	PPA2	0x0
4228	chr4	106344162	106345353	−	PPA2	0x0
4229	chr4	106852779	106853976	+	NPNT	0x0
4230	chr4	107208670	107209801	−	TBCK	0x0
4231	chr4	107868851	107870051	−	DKK2	0x2
4232	chr4	107923941	107925121	−	DKK2	0x2
4233	chr4	109564721	109565921	+	OSTC	0x0
4234	chr4	109760830	109762023	−	COL25A1	0x2
4235	chr4	110104521	110105697	−	COL25A1	0x2
4236	chr4	110608918	110610063	+	CCDC109B	0x0
4237	chr4	110650525	110651689	−	PLA2G12A	0x0
4238	chr4	111068841	111070012	−	EL0VL6	0x2
4239	chr4	113708823	113709979	−	MIR3O2B	0x0
4240	chr4	113785324	113786500	+	ANK2	0x2
4241	chr4	114146722	114148054	+	ANK2	0x2
4242	chr4	114341014	114342181	+	ANK2	0x2
4243	chr4	114437818	114438997	−	CAMK2D	0x0
4244	chr4	114662153	114663347	−	CAMK2D	0x0
4245	chr4	119199757	119201059	+	SNHG8	0x0
4246	chr4	119199757	119201059	+	SNORA24	0x0
4247	chr4	120157972	120159202	+	USP53	0x0
4248	chr4	120476269	120477447	−	PDE5A	0x0
4249	chr4	121587880	121589054	+	PP12613	0x0
4250	chr4	122588643	122590042	−	ANXA5	0x0
4251	chr4	122606909	122608071	−	ANXA5	0x0
4252	chr4	123750558	123751842	+	FGF2	0x0
4253	chr4	128754661	128755882	+	HSPA4L	0x0
4254	chr4	128850808	128851989	−	MFSD8	0x0
4255	chr4	136916515	136917744	−	PCDH18	0x2
4256	chr4	140045828	140047021	−	ELF2	0x0
4257	chr4	140300081	140301298	−	NAA15	0x0
4258	chr4	140427948	140429133	−	SETD7	0x0
4259	chr4	140429601	140430909	−	SETD7	0x0
4260	chr4	140618700	140619799	−	MAML3	0x0
4261	chr4	140805551	140806871	−	MAML3	0x0
4262	chr4	141349704	141350880	−	CLGN	0x0
4263	chr4	142154608	142155762	+	ZNF330	0x0
4264	chr4	143315717	143316925	−	INPP4B	0x1
4265	chr4	144257623	144258821	+	GAB1	0x6
4266	chr4	144270075	144271461	−	FREM3	0x0
4267	chr4	144346149	144347318	+	GAB1	0x6
4268	chr4	146018918	146020143	+	ABCE1	0x2
4269	chr4	146427241	146428425	+	SMAD1	0x0
4270	chr4	146822800	146823918	−	ZNF827	0x0
4271	chr4	149180417	149181814	−	NR3C2	0x0
4272	chr4	149265208	149266372	−	NR3C2	0x0
4273	chr4	149356392	149357576	−	NR3C2	0x0
4274	chr4	151185305	151186711	−	LRBA	0x0
4275	chr4	151871001	151872180	−	LRBA	0x0
4276	chr4	152024415	152025614	+	RPS3A	0x0
4277	chr4	152024415	152025614	+	SNORD73A	0x0
4278	chr4	152041252	152042409	−	SH3D19	0x0
4279	chr4	152591367	152592570	−	PET112	0x0
4280	chr4	153448757	153449897	−	FBXW7	0x1
4281	chr4	154169920	154171208	+	TRIM2	0x0
4282	chr4	154472765	154473974	+	KIAA0922	0x0
4283	chr4	155457250	155458379	−	PLRG1	0x0
4284	chr4	158688599	158689776	−	FAM198B	0x0
4285	chr4	159636841	159637978	−	PPID	0x0
4286	chr4	164045004	164046132	−	NAF1	0x0
4287	chr4	164077750	164078946	−	NAF1	0x0
4288	chr4	166213819	166215040	−	GK3P	0x0
4289	chr4	166263567	166264776	+	MSMO1	0x0
4290	chr4	167021877	167023098	+	TLL1	0x0
4291	chr4	167063135	167064378	+	TLL1	0x0
4292	chr4	169925827	169927030	+	PALLD	0x0
4293	chr4	170332145	170333366	−	NEK1	0x0
4294	chr4	170427527	170428695	−	NEK1	0x0
4295	chr4	174252351	174253786	−	HMGB2	0x0
4296	chr4	174254588	174255755	−	HMGB2	0x0
4297	chr4	175219945	175221126	+	CEP44	0x0
4298	chr4	175275109	175276324	+	CEP44	0x0
4299	chr4	176423626	176424847	+	ADAM29	0x2
4300	chr4	176842074	176843173	−	GPM6A	0x0
4301	chr4	177240631	177241730	+	SPCS3	0x0
4302	chr4	177252721	177253795	+	SPCS3	0x0
4303	chr4	177495908	177497008	−	VEGFC	0x0
4304	chr4	181405460	181406582	−	LINC00290	0x0
4305	chr4	183403106	183404347	+	ODZ3	0x0
4306	chr4	183608768	183609957	+	ODZ3	0x0
4307	chr4	184185650	184186805	+	WWC2	0x0
4308	chr4	184206594	184207757	+	WWC2	0x0
4309	chr4	184236991	184238138	+	WWC2	0x0
4310	chr4	185598395	185599560	+	CCDC111	0x0
4311	chr4	185612026	185613243	+	CCDC111	0x0
4312	chr4	186284166	186285356	+	SNX25	0x0
4313	chr4	187548781	187550336	−	FAT1	0x1
4314	chr4	187595179	187596294	−	FAT1	0x1
4315	chr4	187627324	187628579	−	FAT1	0x1
4316	chr4	187628672	187630961	−	FAT1	0x1
4317	chr5	256042	257241	+	SDHA	0x1
4318	chr5	465016	466156	+	EXOC3	0x0
4319	chr5	475184	476283	+	EXOC3	0x0
4320	chr5	616400	617529	+	CEP72	0x0
4321	chr5	619661	620917	+	CEP72	0x0
4322	chr5	855260	856450	−	ZDHHC11	0x0
4323	chr5	881928	883115	−	BRD9	0x0
4324	chr5	984575	985775	−	LOC100506688	0x0
4325	chr5	1011265	1012552	+	NKD2	0x0
4326	chr5	1059288	1060478	+	NKD2	0x0
4327	chr5	1317484	1318925	−	CLPTM1L	0x0
4328	chr5	2099419	2100621	+	NDUFS6	0x0
4329	chr5	5433872	5435049	+	KIAA0947	0x0
4330	chr5	6367854	6369079	+	MED10	0x0
4331	chr5	6599311	6600462	−	NSUN2	0x0
4332	chr5	6732256	6733453	+	PAPD7	0x0
4333	chr5	6742830	6744075	+	PAPD7	0x0
4334	chr5	6847884	6849102	−	MIR4278	0x0
4335	chr5	7054525	7055680	−	MIR4454	0x0
4336	chr5	10277925	10279202	−	CMBL	0x0
4337	chr5	10374162	10375376	+	MARCH6	0x0
4338	chr5	10379681	10380780	+	MARCH6	0x0
4339	chr5	10400598	10401855	+	MARCH6	0x0
4340	chr5	10415135	10416313	+	MARCH6	0x0
4341	chr5	10425959	10427183	+	MARCH6	0x0
4342	chr5	14420879	14422105	+	TRIO	0x0
4343	chr5	14482958	14484167	+	TRIO	0x0
4344	chr5	14508432	14509594	+	TRIO	0x0
4345	chr5	14701374	14702535	−	ANKH	0x0
4346	chr5	14750666	14751845	−	ANKH	0x0
4347	chr5	15822964	15824180	+	FBXL7	0x0
4348	chr5	18800477	18801690	+	BASP1	0x0
4349	chr5	20304100	20305276	−	CDH18	0x4
4350	chr5	21527696	21528894	+	GUSBP1	0x0
4351	chr5	31455998	31457175	−	DROSHA	0x2
4352	chr5	31488619	31489794	−	DROSHA	0x2
4353	chr5	32124537	32125869	−	GOLPH3	0x0
4354	chr5	32143298	32144538	−	GOLPH3	0x0
4355	chr5	32378698	32379827	−	ZFR	0x0
4356	chr5	32601050	32602364	+	SUB1	0x0
4357	chr5	33161873	33163111	+	LOC340113	0x0
4358	chr5	33452823	33453991	+	TARS	0x0
4359	chr5	34068024	34069192	−	C1QTNF3	0x0
4360	chr5	34801788	34803022	+	RAI14	0x0
4361	chr5	36146478	36147695	−	MIR580	0x0
4362	chr5	36931288	36932498	+	NIPBL	0x0
4363	chr5	37107160	37108354	−	C5orf42	0x0
4364	chr5	37290557	37291656	−	NUP155	0x0
4365	chr5	37644395	37645575	+	WDR70	0x0
4366	chr5	38966651	38967862	−	RICTOR	0x0
4367	chr5	40714019	40715191	−	PE33	0x0
4368	chr5	40834076	40835225	−	RPL37	0x0
4369	chr5	41920550	41921732	+	C5orf51	0x0
4370	chr5	43290478	43291600	−	HMGCS1	0x0
4371	chr5	44816488	44817669	+	MRPS30	0x0
4372	chr5	53348060	53349257	−	ARL15	0x0
4373	chr5	54964571	54965747	−	SLC38A9	0x0
4374	chr5	55281035	55282211	−	IL6ST	0x2
4375	chr5	56239517	56240829	−	MIER3	0x2
4376	chr5	56464363	56465567	−	MIER3	0x2
4377	chr5	60163431	60164583	−	ERCC8	0x0
4378	chr5	60195168	60196367	−	ERCC8	0x0
4379	chr5	60280264	60281431	+	NDUFAF2	0x0
4380	chr5	60454911	60456125	−	C5orf43	0x0
4381	chr5	60629614	60630713	+	ZSWIM6	0x0
4382	chr5	60778117	60779343	+	ZSWIM6	0x0
4383	chr5	60838057	60839254	+	ZSWIM6	0x0
4384	chr5	64017997	64019153	−	SREK1IP1	0x0
4385	chr5	64826677	64827834	−	CENPK	0x0
4386	chr5	64854223	64855425	−	CENPK	0x0
4387	chr5	65474521	65475620	+	SREK1	0x0
4388	chr5	65929854	65931080	+	MAST4	0x0
4389	chr5	68169262	68170459	+	SLC30A5	0x0
4390	chr5	68470301	68471848	+	CCNB1	0x0
4391	chr5	68534620	68535809	+	CDK7	0x0
4392	chr5	71146171	71147505	+	CARTPT	0x0
4393	chr5	71501197	71502296	+	MAP1B	0x2
4394	chr5	71558941	71560151	−	MRPS27	0x0
4395	chr5	72153426	72154546	+	TNPO1	0x2
4396	chr5	72188374	72189602	+	TNPO1	0x2
4397	chr5	72206009	72207217	+	TNPO1	0x2
4398	chr5	72293664	72294858	+	FCHO2	0x0
4399	chr5	72798331	72799514	+	BTF3	0x0
4400	chr5	73923248	73924390	−	ENC1	0x0
4401	chr5	75630962	75632158	−	F2RL2	0x2
4402	chr5	75775909	75777085	−	F2RL2	0x2
4403	chr5	76375769	76376916	−	SNORA47	0x0
4404	chr5	76727954	76729712	−	WDR41	0x0
4405	chr5	77301561	77302684	−	AP3B1	0x0
4406	chr5	77435096	77436266	−	AP3B1	0x0
4407	chr5	77528492	77529643	−	AP3B1	0x0
4408	chr5	78734358	78735466	−	HOMER1	0x0
4409	chr5	79548465	79549683	+	SPZ1	0x0
4410	chr5	80183593	80184748	+	MSH3	0x2
4411	chr5	80484785	80485962	−	LOC100131067	0x0
4412	chr5	80628317	80629455	−	ACOT12	0x0
4413	chr5	81570830	81571946	−	RPS23	0x0
4414	chr5	81573146	81574245	−	RPS23	0x0
4415	chr5	82254994	82256171	−	TMEM167A	0x0
4416	chr5	82359469	82360601	−	SCARNA18	0x0
4417	chr5	86569424	86570609	+	RASA1	0x2
4418	chr5	89768753	89769931	−	M8LAC2	0x0
4419	chr5	90105888	90107164	+	GPR98	0x0
4420	chr5	92929548	92930740	+	NR2F1	0x0
4421	chr5	93018311	93019965	−	POUSF2	0x0
4422	chr5	93131269	93132417	−	FAM172A	0x0
4423	chr5	94173902	94175063	−	MCTP1	0x0
4424	chr5	95158511	95159640	+	RHOBTB3	0x0
4425	chr5	95239923	95241132	−	ELL2	0x0
4426	chr5	96323354	96324453	+	INPEP	0x0
4427	chr5	100068452	100069649	+	FAM174A	0x0
4428	chr5	101637845	101639040	+	PAM	0x0
4429	chr5	102087133	102088329	−	SLCO6A1	0x0
4430	chr5	102212164	102213379	+	PAM	0x0
4431	chr5	107002182	107003311	−	EFNA5	0x1
4432	chr5	108229675	108230841	−	HP07349	0x0
4433	chr5	108349997	108351209	−	HP07349	0x0
4434	chr5	109034853	109036078	−	PJA2	0x0
4435	chr5	109146662	109147860	+	MAN2A1	0x0
4436	chr5	109930841	109932041	+	TMEM232	0x0
4437	chr5	110458675	110459862	+	WDR36	0x0
4438	chr5	111496683	111497883	+	EPB41L4A-AS1	0x0
4439	chr5	111496683	111497883	+	SNORA13	0x0
4440	chr5	112349145	112350420	+	DCP2	0x0
4441	chr5	112382879	112384028	−	MCC	0x1
4442	chr5	112599748	112600940	−	MCC	0x1
4443	chr5	118172992	118174184	−	DTWD2	0x0
4444	chr5	118417262	118418446	+	DMXL1	0x0
4445	chr5	118499717	118500922	+	DMXL1	0x0
4446	chr5	122358764	122359921	−	PPIC	0x0
4447	chr5	122698012	122699206	−	CEP120	0x0
4448	chr5	122880801	122882021	+	CSNK1G3	0x0
4449	chr5	122990432	122991632	+	CSNK1G3	0x0
4450	chr5	123981877	123983264	−	ZNF608	0x0
4451	chr5	123998470	123999607	−	ZNF608	0x0
4452	chr5	126112381	126113578	+	LMNB1	0x0
4453	chr5	126153331	126154530	+	LMNB1	0x0
4454	chr5	126889467	126890663	+	PRRC1	0x0
4455	chr5	127276736	127277912	−	FLJ33630	0x0
4456	chr5	129449539	129450732	+	CHSY3	0x0
<4457	chr5	130524747	130525947	+	LYRM7	0x0
4458	chr5	130746679	130747856	−	RAPGEF6	0x0
4459	chr5	130760870	130762039	−	RAPGEF6	0x0
4460	chr5	130771334	130772508	−	RAPGEF6	0x0
4461	chr5	130959540	130960717	−	RAPGEF6	0x0
4462	chr5	130977720	130978819	−	FNIP1	0x0
4463	chr5	131515897	131517099	+	PDLIM4	0x1
4464	chr5	131803299	131804500	+	C5orf56	0x0
4465	chr5	132202774	132203870	+	UQCRQ	0x0
4466	chr5	133307460	133308834	−	VDAC1	0x0
4467	chr5	133311749	133312912	−	VDAC1	0x0
4468	chr5	133492617	133493834	−	SKP1	0x0
4469	chr5	133532291	133533413	−	PPP2CA	0x0
4470	chr5	134076563	134077772	+	CAMLG	0x0
4471	chr5	134115176	134117473	+	DDX46	0x0
4472	chr5	134159669	134160855	+	DDX46	0x0
4473	chr5	134259234	134260405	+	MIR4461	0x0
4474	chr5	134262142	134263369	−	PITX1	0x0
4475	chr5	134355468	134356654	−	PITX1	0x0
4476	chr5	134570673	134571870	+	CATSPER3	0x0
4477	chr5	134669500	134670677	−	H2AFY	0x0
4478	chr5	137033418	137034620	−	KLHL3	0x0
4479	chr5	137087973	137089077	−	HNRNPAO	0x0
4480	chr5	137289730	137290854	−	FAM13B	0x0
4481	chr5	137666391	137667527	−	CDC25C	0x2
4482	chr5	137771267	137772439	+	KDM3B	0x1
4483	chr5	137781466	137783078	+	REEP2	0x0
4484	chr5	137842197	137843338	−	ETF1	0x0
4485	chr5	137896165	137897367	−	HSPA9	0x0
4486	chr5	137896165	137897367	−	SNORD63	0x0
4487	chr5	138119261	138120454	+	CTNNA1	0x0
4488	chr5	138613928	138615224	+	MATR3	0x0
4489	chr5	138613928	138615224	+	SNHG4	0x0
4490	chr5	138613928	138615224	+	SNORA74A	0x0
4491	chr5	138664683	138665785	+	MATR3	0x0
4492	chr5	138697052	138698264	+	PAIP2	0x0
4493	chr5	138955660	138956759	+	UBE2D2	0x0
4494	chr5	139907953	139909087	+	ANKHD1	0x0
4495	chr5	139907953	139909087	+	ANKHD1-EIF4EBP3	0x0
4496	chr5	139935676	139936843	−	SRA1	0x0
4497	chr5	139942922	139944119	−	APBB3	0x0
4498	chr5	139947150	139948368	+	SLC35A4	0x0
4499	chr5	140026517	140027657	−	NDUFA2	0x0
4500	chr5	140090322	140091532	+	VTRNA1-1	0x0
4501	chr5	140097951	140099191	+	VTRNA1-2	0x0
4502	chr5	140105202	140106473	+	VTRNA1-3	0x0
4503	chr5	140697652	140699013	−	TAF7	0x0
4504	chr5	140882980	140884167	+	PCDHGA1	0x0
4505	chr5	140882980	140884167	+	PCDHGA10	0x0
4506	chr5	140882980	140884167	+	PCDHGA11	0x0
4507	chr5	140882980	140884167	+	PCDHGA12	0x0
4508	chr5	140882980	140884167	+	PCDHGA2	0x0
4509	chr5	140882980	140884167	+	PCDHGA3	0x0
4510	chr5	140882980	140884167	+	PCDHGA4	0x0
4511	chr5	140882980	140884167	+	PCDHGA5	0x0
4512	chr5	140882980	140884167	+	PCDHGA6	0x0
4513	chr5	140882980	140884167	+	PCDHGA7	0x0
4514	chr5	140882980	140884167	+	PCDHGA8	0x0
4515	chr5	140882980	140884167	+	PCDHGA9	0x0
4516	chr5	140882980	140884167	+	PCDHGB1	0x0
4517	chr5	140882980	140884167	+	PCDHGB2	0x0
4518	chr5	140882980	140884167	+	PCDHGB3	0x0
4519	chr5	140882980	140884167	+	PCDHGB4	0x0
4520	chr5	140882980	140884167	+	PCDHGB5	0x0
4521	chr5	140882980	140884167	+	PCDHGB6	0x0
4522	chr5	140882980	140884167	+	PCDHGB7	0x0
4523	chr5	140882980	140884167	+	PCDHGC3	0x0
4524	chr5	140882980	140884167	+	PCDHGC4	0x0
4525	chr5	140882980	140884167	+	PCDHGC5	0x2
4526	chr5	140894240	140895404	−	DIAPH1	0x2
4527	chr5	140958099	140959290	−	DIAPH1	0x2
4528	chr5	141005206	141006359	−	HDAC3	0x1
4529	chr5	141313659	141314784	+	KIAA0141	0x0
4530	chr5	141379710	141380830	−	GNPDA1	0x0
4531	chr5	142659520	142660619	−	NR3C1	0x0
4532	chr5	145485049	145486259	−	PLAC8L1	0x0
4533	chr5	145828942	145830154	+	TCERG1	0x2
4534	chr5	145934974	145936167	+	TCERG1	0x2
4535	chr5	146770912	146772858	−	DPYSL3	0x0
4536	chr5	147695170	147696363	+	SPINK7	0x1
4537	chr5	149221294	149222492	+	PPARGC1B	0x0
4538	chr5	149379189	149380405	+	HMGXB3	0x0
4539	chr5	149391310	149392467	+	HMGXB3	0x0
4540	chr5	149409668	149410825	+	HMGXB3	0x0
4541	chr5	149823257	149824472	−	RPS14	0x0
4542	chr5	149826726	149827839	−	RPS14	0x0
4543	chr5	149933323	149934522	+	NDST1	0x0
4544	chr5	150088157	150089605	−	DCTN4	0x0
4545	chr5	150305903	150307127	+	IRGM	0x0
4546	chr5	151166977	151168088	+	G3BP1	0x2
4547	chr5	151176282	151177428	+	G3BP1	0x2
4548	chr5	151183068	151184445	+	G3BP1	0x2
4549	chr5	151988029	151989202	+	G3BP1	0x2
4550	chr5	154184861	154185960	+	LARP1	0x0
4551	chr5	154194245	154195970	+	LARP1	0x0
4552	chr5	155271898	155273116	+	SGCD	0x0
4553	chr5	157258473	157259663	−	CLINT1	0x0
4554	chr5	157403274	157404503	−	CLINT1	0x0
4555	chr5	159519658	159520837	−	PWWP2A	0x0
4556	chr5	162917770	162918943	+	HMMR	0x0
4557	chr5	164286793	164287987	+	MAT2B	0x0
4558	chr5	167979735	167980834	−	PANK3	0x0
4559	chr5	170532740	170533963	+	RANBP17	0x2
4560	chr5	170631767	170632976	+	RANBP17	0x2
4561	chr5	170650569	170651816	+	RANBP17	0x2
4562	chr5	170814307	170815505	+	NPM1	0x2
4563	chr5	170833000	170834240	+	NPM1	0x2
4564	chr5	170836987	170838202	+	NPM1	0x2
4565	chr5	170864262	170865494	+	FGF18	0x0
4566	chr5	171636089	171637261	−	UBTD2	0x0
4567	chr5	172402266	172403402	+	RPL26L1	0x0
4568	chr5	172447180	172448424	+	ATP6V0E1	0x0
4569	chr5	172447180	172448424	+	SNORA74B	0x0
4570	chr5	174541243	174542729	−	FLI16171	0x0
4571	chr5	174954262	174955476	+	SFXN1	0x0
4572	chr5	175046803	175047922	−	DRD1	0x0
4573	chr5	176348311	176349451	−	UIMC1	0x0
4574	chr5	176729779	176730956	−	RAB24	0x2
4575	chr5	176868941	176870106	+	GRK6	0x0
4576	chr5	176881538	176882733	+	PRR7	0x0
4577	chr5	176883596	176884716	−	DBN1	0x2
4578	chr5	176964393	176966567	−	FAM193B	0x0
4579	chr5	177058987	177060287	−	LOC202181	0x0
4580	chr5	177310372	177311573	+	LOC728554	0x0
4581	chr5	177379634	177380812	+	FAM153C	0x0
4582	chr5	177656564	177657732	−	AGXT2L2	0x0
4583	chr5	179049534	179050703	−	HNRNPH1	0x0
4584	chr5	179132092	179133317	+	CANX	0x0
4585	chr5	179155733	179157832	+	CANX	0x0
4586	chr5	179251620	179252771	+	SQSTM1	0x0
4587	chr5	179673716	179674848	−	MAPK9	0x0
4588	chr5	180206560	180207717	−	MGAT1	0x0
4589	chr5	180528261	180529516	+	BTNL9	0x0
4590	chr5	180634178	180635408	+	TRIM41	0x0
4591	chr5	180644693	180645829	−	MIR4638	0x0
4592	chr5	180665592	180666691	−	GNB2L1	0x0
4593	chr5	180667997	180669448	−	GN82L1	0x0
4594	chr5	180667997	180669448	−	SNORD96A	0x0
4595	chr5	180669745	180671450	−	GN82L1	0x0
4596	chr5	180669745	180671450	−	SNORD95	0x0
4597	chr6	350525	351808	+	DUSP22	0x1
4598	chr6	694363	695593	+	IRF4	0x2
4599	chr6	1392055	1393297	+	FOXF2	0x0
4600	chr6	2249565	2250764	+	LOC100508120	0x0
4601	chr6	2959958	2961063	−	SERPINB6	0x0
4602	chr6	2999751	3000981	+	NQO2	0x0
4603	chr6	3224108	3225372	−	TUBB2B	0x0
4604	chr6	3343107	3344230	+	SLC22A23	0x0
4605	chr6	4061321	4062476	+	PRPF4B	0x2
4606	chr6	4427628	4428908	+	CDYL	0x2
4607	chr6	4891386	4893097	+	CDYL	0x2
4608	chr6	5305109	5306287	−	LYRM4	0x0
4609	chr6	5819194	5820380	+	FARS2	0x0
4610	chr6	6006440	6007652	−	NRN1	0x0
4611	chr6	7281986	7283116	−	SSR1	0x0
4612	chr6	7289208	7290341	−	SSR1	0x0
4613	chr6	7312770	7313892	−	SSR1	0x0
4614	chr6	7338944	7340205	−	CAGE1	0x0
4615	chr6	7417091	7418291	+	RIOK1	0x0
4616	chr6	7567486	7568687	+	DSP	0x0
4617	chr6	10397277	10398503	−	TFAP2A	0x1
4618	chr6	10790794	10791948	+	TMEM14B	0x0
4619	chr6	11120447	11121644	+	C6orf228	0x0
4620	chr6	11135447	11136546	+	C6orf228	0x0
4621	chr6	12094830	12095971	+	HIVEP1	0x0
4622	chr6	12513934	12515138	+	PHACTR1	0x0
4623	chr6	13213750	13214999	+	PHACTR1	0x0
4624	chr6	13374363	13375494	−	GFOD1	0x0
4625	chr6	13486586	13487751	−	GFOD1	0x0
4626	chr6	13646093	13647202	−	RANBP9	0x0
4627	chr6	13787360	13788567	−	CCDC90A	0x0
4628	chr6	15011581	15012776	+	JAR1D2	0x2
4629	chr6	15416602	15417810	+	JARID2	0x2
4630	chr6	16326605	16327827	−	ATXN1	0x0
4631	chr6	16747172	16748334	−	ATXN1	0x0
4632	chr6	17615189	17616505	−	NUP153	0x0
4633	chr6	18224189	18225654	−	DEK	0x2
4634	chr6	18264094	18265258	−	DEK	0x2
4635	chr6	19839163	19840388	+	ID4	0x1
4636	chr6	20452761	20453860	+	E2F3	0x2
4637	chr6	20556060	20557162	+	CDKAL1	0x0
4638	chr6	21593746	21594950	+	SOX4	0x0
4639	chr6	21595334	21596486	+	SOX4	0x0
4640	chr6	24417797	24418997	+	MRS2	0x0
4641	chr6	24718988	24720133	−	C6orf62	0x0
4642	chr6	26020508	26021702	+	HIST1H3A	0x0
4643	chr6	26026615	26027821	−	HIST1H4B	0x0
4644	chr6	26031448	26032740	−	HIST1H3B	0x0
4645	chr6	26056020	26057248	−	HIST1H1C	0x2
4646	chr6	26103864	26105124	+	H1ST1H4C	0x0
4647	chr6	26156035	26157248	+	HIST1H1E	0x2
4648	chr6	26157864	26159045	+	HIST1H2BD	0x0
4649	chr6	26198776	26199974	−	HIST1H2AD	0x0
4650	chr6	26198776	26199974	−	HIST1H3D	0x0
4651	chr6	26204313	26205679	+	HIST1H4E	0x0
4652	chr6	26216601	26217833	+	HIST1H2AE	0x0
4653	chr6	26250095	26251233	−	HIST1H3F	0x0
4654	chr6	26284906	26286305	−	HIST1H4H	0x0
4655	chr6	26305137	26306335	−	HIST1H4H	0x0
4656	chr6	26327842	26329088	+	BTN3A2	0x0
4657	chr6	26520899	26522108	+	HCG11	0x0
4658	chr6	26537187	26538396	+	HMGN4	0x0
4659	chr6	26553894	26554993	+	HMGN4	0x0
4660	chr6	26556236	26557446	+	HMGN4	0x0
4661	chr6	26568500	26569739	+	HMGN4	0x0
4662	chr6	26575282	26576489	+	ABT1	0x0
4663	chr6	26576788	26577992	+	ABT1	0x0
4664	chr6	26594507	26595750	+	ABT1	0x0
4665	chr6	27077095	27078239	−	HIST1H2BJ	0x0
4666	chr6	27100256	27101388	+	HIST1H2AG	0x0
4667	chr6	27114034	27115196	−	HIST1H2BK	0x0
4668	chr6	27125338	27126535	+	MIR3143	0x0
4669	chr6	27177100	27178332	+	PRSS16	0x0
4670	chr6	27181083	27182248	−	HIST1H2BK	0x0
4671	chr6	27182391	27183627	+	PRSS16	0x0
4672	chr6	27197707	27198928	−	POM121L2	0x0
4673	chr6	27261107	27262319	+	VN1R10P	0x0
4674	chr6	27262686	27263839	+	VN1R10P	0x0
4675	chr6	27265242	27266405	+	VN1R10P	0x0
4676	chr6	27470978	27472096	+	ZNF391	0x2
4677	chr6	27514942	27516154	−	ZNF184	0x0
4678	chr6	27520641	27521851	−	ZNF184	0x0
4679	chr6	27550661	27551841	−	ZNF184	0x0
4680	chr6	27569815	27570892	−	ZNF184	0x0
4681	chr6	27572845	27574055	−	ZNF184	0x0
4682	chr6	27618069	27619288	−	HIST1H2BL	0x0
4683	chr6	27637768	27638977	−	HIST1H2BL	0x0
4684	chr6	27758556	27759782	−	HIST1H2BL	0x0
4685	chr6	27860016	27861423	−	HIST1H2AM	0x0
4686	chr6	27860839	27861988	+	HIST1H2BO	0x2
4687	chr6	28180242	28181509	+	ZNF193	0x0
4688	chr6	28426989	28428187	−	ZSCAN23	0x0
4689	chr6	28625465	28626614	−	SCAND3	0x0
4690	chr6	28641012	28642197	−	SCAND3	0x0
4691	chr6	28663157	28664356	−	SCAND3	0x0
4692	chr6	28677791	28678990	+	GPX5	0x0
4693	chr6	28696501	28697715	+	GPX5	0x0
4694	chr6	28702649	28703851	−	LOC401242	0x0
4695	chr6	28714933	28716164	+	GPX5	0x0
4696	chr6	28725595	28726811	−	LOC401242	0x0
4697	chr6	28757006	28758172	−	LOC401242	0x0
4698	chr6	28769969	28771216	−	LOC401242	0x0
4699	chr6	28784408	28785655	−	LOC401242	0x0
4700	chr6	28863440	28864678	−	TRIM27	0x2
4701	chr6	28865423	28866591	−	TRIM27	0x2
4702	chr6	28908284	28909530	+	LOC100129636	0x0
4703	chr6	28911814	28913011	+	LOC100129636	0x0
4704	chr6	28918286	28919467	+	LOC100129636	0x0
4705	chr6	29593377	29594477	−	GABBR1	0x2
4706	chr6	29912705	29913935	+	HLA-A	0x2
4707	chr6	30174258	30175638	−	TRIM26	0x0
4708	chr6	30513886	30515122	−	GNL1	0x0
4709	chr6	30680109	30681208	−	MDC1	0x0
4710	chr6	30681230	30682456	−	MDC1	0x0
4711	chr6	30691823	30693561	+	TUBB	0x2
4712	chr6	30831650	30832824	+	DDR1	0x0
4713	chr6	30846909	30848085	+	DDR1	0x0
4714	chr6	31130402	31131596	+	TCF19	0x0
4715	chr6	31496068	31497234	−	ATP6V1G2-DDX39B	0x0
4716	chr6	31496068	31497234	−	DDX39B	0x0
4717	chr6	31501739	31502906	−	ATP6V1G2-DDX39B	0x0
4718	chr6	31501739	31502906	−	DDX39B	0x0
4719	chr6	31507750	31508843	−	ATP6V1G2-DDX39B	0x0
4720	chr6	31507750	31508843	−	DDX39B	0x0
4721	chr6	31588657	31589786	+	PRRC2A	0x0
4722	chr6	31590298	31591538	+	PRRC2A	0x0
4723	chr6	31590298	31591538	+	SNORA38	0x0
4724	chr6	31613730	31614837	−	BAG6	0x0
4725	chr6	31703631	31704808	−	CLIC1	0x0
4726	chr6	31746849	31748039	−	VARS	0x0
4727	chr6	31760008	31761205	−	VARS	0x0
4728	chr6	31782864	31784065	+	HSPA1A	0x0
4729	chr6	31784919	31786234	+	HSPA1A	0x0
4730	chr6	31797179	31798469	+	HSPA1B	0x0
4731	chr6	31804278	31805485	+	C6orf48	0x0
4732	chr6	31804278	31805485	+	SNORD52	0x0
4733	chr6	32086135	32087386	−	ATF6B	0x0
4734	chr6	32148451	32149554	+	RNF5	0x0
4735	chr6	32148451	32149554	+	RNF5P1	0x0
4736	chr6	33239916	33241022	+	RPS18	0x0
4737	chr6	33243018	33244197	+	RPS18	0x0
4738	chr6	33266967	33268141	−	RGL2	0x0
4739	chr6	33266967	33268141	−	TAPBP	0x0
4740	chr6	33654767	33655866	+	ITPR3	0x2
4741	chr6	33738948	33740183	−	LEMD2	0x0
4742	chr6	34204449	34205642	+	HMGA1	0x2
4743	chr6	34213068	34214379	+	HMGA1	0x2
4744	chr6	34249271	34250682	−	NUDT3	0x0
4745	chr6	34249271	34250682	−	RPS10-NUDT3	0x0
4746	chr6	34388259	34389415	−	RPS10	0x0
4747	chr6	34388259	34389415	−	RPS10-NUDT3	0x0
4748	chr6	34390262	34391440	−	RPS10	0x0
4749	chr6	34390262	34391440	−	RPS10-NUDT3	0x0
4750	chr6	34556452	34557600	−	C6orf106	0x0
4751	chr6	34826547	34827779	+	UHRF1BP1	0x0
4752	chr6	35032311	35033701	+	ANKS1A	0x0
4753	chr6	35451550	35452727	−	TEAD3	0x0
4754	chr6	35523396	35524603	+	RPL10A	0x0
4755	chr6	35853153	35854414	−	SRPK1	0x0
4756	chr6	36198642	36199909	+	BRPF3	0x0
4757	chr6	36569808	36571036	+	SRSF3	0x2
4758	chr6	36894856	36896000	+	C6orf89	0x0
4759	chr6	37358228	37359440	+	RNF8	0x0
4760	chr6	38041182	38042392	+	ZFAND3	0x0
4761	chr6	41761912	41763042	−	USP49	0x0
4762	chr6	42236613	42237790	−	TRERF1	0x0
4763	chr6	42423307	42424509	+	UBR2	0x0
4764	chr6	42856085	42857313	+	RPL7L1	0x0
4765	chr6	42923667	42925068	−	PEX6	0x0
4766	chr6	42988024	42989312	−	KLHDC3	0x0
4767	chr6	43025492	43027669	−	MRPL2	0x0
4768	chr6	43037667	43038876	+	KLC4	0x0
4769	chr6	43095792	43096991	+	PTK7	0x0
4770	chr6	43171690	43172872	+	CUL9	0x0
4771	chr6	44081319	44082523	−	MRPL14	0x0
4772	chr6	44094272	44095453	−	MRPL14	0x0
4773	chr6	44219220	44220481	+	HSP90AB1	0x2
4774	chr6	44266391	44267567	−	AARS2	0x0
4775	chr6	44408477	44410722	+	CDC5L	0x0
4776	chr6	44995610	44996776	−	SUPT3H	0x0
4777	chr6	46111643	46112793	+	ENPP4	0x0
4778	chr6	46622408	46623507	+	SLC25A27	0x0
4779	chr6	47251283	47252411	−	TNFRSF21	0x0
4780	chr6	47253341	47254576	−	TNFRSF21	0x0
4781	chr6	52349296	52350448	+	EFHC1	0x0
4782	chr6	52849480	52850704	−	GSTA4	0x0
4783	chr6	52855044	52856169	−	GSTA4	0x0
4784	chr6	52859885	52861330	+	FBXO9	0x0
4785	chr6	52957213	52958430	+	FBXO9	0x0
4786	chr6	53083552	53084753	+	FBXO9	0x0
4787	chr6	53132185	53133289	−	ELOVL5	0x0
4788	chr6	56399463	56400610	−	OST	0x2
4789	chr6	57034314	57035512	+	ZNF451	0x0
4790	chr6	57053896	57055230	−	RAB23	0x2
4791	chr6	63921356	63922581	+	PTP4A1	0x0
4792	chr6	64290668	64291881	+	PTP4A1	0x0
4793	chr6	71225073	71226176	+	FAM135A	0x0
4794	chr6	73448473	73449706	+	KCNQ5	0x2
4795	chr6	74197008	74198113	−	EEF1A1	0x1
4796	chr6	74227963	74229055	−	EEF1A1	0x1
4797	chr6	74229688	74230876	−	EEF1A1	0x1
4798	chr6	74309553	74310681	−	SLC17A5	0x2
4799	chr6	75946972	75948118	−	COX7A2	0x0
4800	chr6	77993678	77994796	−	HTR1B	0x0
4801	chr6	79665318	79666472	−	PHIP	0x2
4802	chr6	79769656	79770833	−	PHIP	0x2
4803	chr6	80656541	80657733	−	ELOVL4	0x0
4804	chr6	80751306	80752707	+	TTK	0x2
4805	chr6	83706974	83708136	−	UBE3D	0x0
4806	chr6	83787687	83788905	+	DOPEY1	0x0
4807	chr6	84942245	84943434	−	KIAA1009	0x0
4808	chr6	86323454	86325410	−	SYNCRIP	0x0
4809	chr6	86333179	86334327	−	SYNCRIP	0x0
4810	chr6	86339754	86340907	−	SYNCRIP	0x0
4811	chr6	86386454	86387828	−	SNHG5	0x0
4812	chr6	86386454	86387828	−	SNORD50A	0x1
4813	chr6	86385454	86387828	−	SNORD50B	0x0
4814	chr6	87896838	87898031	+	ZNF292	0x0
4815	chr6	88268955	88270163	−	RARS2	0x0
4816	chr6	88271871	88273026	−	RARS2	0x0
4817	chr6	89512421	89513595	−	RNGTT	0x0
4818	chr6	89772705	89773936	−	SRSF12	0x0
4819	chr6	90036427	90037576	−	UBE2J1	0x0
4820	chr6	90103175	90104299	−	RRAGD	0x0
4821	chr6	90180489	90181711	+	ANKRD6	0x0
4822	chr6	90190795	90191990	+	ANKRD6	0x0
4823	chr6	90319964	90321150	+	ANKRD6	0x0
4824	chr6	90352660	90354462	−	MDN1	0x0
4825	chr6	90377219	90378421	−	MDN1	0x0
4826	chr6	91224962	91226062	−	MAP3K7	0x0
4827	chr6	91327958	91329132	+	MIR4464	0x0
4828	chr6	94045719	94046894	−	EPHA7	0x2
4829	chr6	94268127	94269325	+	TSG1	0x0
4830	chr6	97632526	97633664	−	MMS22L	0x0
4831	chr6	97683639	97684802	−	IMMS22L	0x0
4832	chr6	97685918	97687017	−	MMS22L	0x0
4833	chr6	97719552	97720728	−	MMS22L	0x0
4834	chr6	100028547	100029746	−	CCNC	0x1
4835	chr6	100905416	100906563	−	SIM1	0x0
4836	chr6	101135519	101136729	−	ASCC3	0x0
4837	chr6	101146910	101148133	−	ASCC3	0x0
4838	chr6	105544496	105545608	−	BVES	0x0
4839	chr6	106730913	106732080	−	ATG5	0x0
4840	chr6	106896710	106897932	+	AIM1	0x4
4841	chr6	107388384	107389560	−	BEND3	0x0
4842	chr6	107969104	107970332	+	SOBP	0x0
4843	chr6	108984597	108986174	+	FOXO3	0x1
4844	chr6	109688249	109689435	−	CD164	0x0
4845	chr6	111193860	111195060	+	AMD1	0x0
4846	chr6	111210899	111212106	+	AMD1	0x0
4847	chr6	111588017	111589142	+	KIAA1919	0x0
4848	chr6	111653808	111654975	−	REV3L	0x0
4849	chr6	111793412	111794582	−	REV3L	0x0
4850	chr6	111904428	111905605	+	TRAF3IP2-AS1	0x0
4851	chr6	111982194	111983390	−	FYN	0x0
4852	chr6	113292154	113293373	+	RFPL4B	0x0
4853	chr6	114178112	114179330	+	MARCKS	0x0
4854	chr6	114181875	114183039	+	MARCKS	0x0
4855	chr6	116579247	116580527	−	TSPYL4	0x0
4856	chr6	116598668	116599891	−	TSPYL1	0x0
4857	chr6	117034886	117036007	+	KPNA5	0x2
4858	chr6	118031778	118032913	+	NUS1	0x0
4859	chr6	118332249	118333446	+	SLC35F1	0x0
4860	chr6	118554121	118555276	−	CEP85L	0x0
4861	chr6	119177072	119178279	−	MCM9	0x0
4862	chr6	119393192	119394423	−	MIR548B	0x0
4863	chr6	121007221	121008447	+	GJA1	0x1
4864	chr6	121769727	121770978	+	GJA1	0x1
4865	chr6	121900967	121902148	−	C6orf170	0x2
4866	chr6	123065973	123067206	+	PKIB	0x0
4867	chr6	124217186	124218234	+	NKAIN2	0x0
4868	chr6	125596639	125597850	−	HDDC2	0x0
4869	chr6	126299287	126300490	+	HINT3	0x0
4870	chr6	126359698	126360815	+	TRMT11	0x0
4871	chr6	126371294	126372445	+	TRMT11	0x0
4872	chr6	126500603	126501839	+	TRMT11	0x0
4873	chr6	126524483	126525677	+	CENPW	0x0
4874	chr6	131215651	131216815	−	EPB41L2	0x0
4875	chr6	131337192	131338291	−	EPB41L2	0x0
4876	chr6	131517695	131518893	+	AKAP7	0x0
4877	chr6	131978592	131979749	+	ENPP3	0x0
4878	chr6	132381098	132382233	+	LOC100507254	0x0
4879	chr6	133135538	133137071	+	RPS12	0x0
4880	chr6	133135538	133137071	+	SNORD101	0x0
4881	chr6	133137377	133138573	+	RPS12	0x0
4882	chr6	133137377	133138573	+	SNORA33	0x0
4883	chr6	133137377	133138573	+	SNORD100	0x0
4884	chr6	135776476	135777666	−	AHI1	0x0
4885	chr6	135792205	135793369	−	AHI1	0x0
4886	chr6	136580786	136583058	−	BCLAF1	0x2
4887	chr6	136609769	136610922	−	BCLAF1	0x2
4888	chr6	136950837	136951945	+	PEX7	0x0
4889	chr6	136985366	136986559	−	MAP3K5	0x2
4890	chr6	137516718	137517919	+	IFNGR1	0x0
4891	chr6	138411876	138413053	−	PERP	0x0
4892	chr6	139471071	139472211	+	HECA	0x1
4893	chr6	143770410	143771612	+	PEX3	0x0
4894	chr6	144024630	144025793	+	PHACTR2	0x0
4895	chr6	144080177	144081352	+	PHACTR2	0x0
4896	chr6	144092907	144094059	+	PHACTR2	0x0
4897	chr6	144415589	144416776	−	SF3B5	0x0
4898	chr6	144691525	144692844	−	SF3B5	0x0
4899	chr6	145503291	145504468	+	UTRN	0x0
4900	chr6	148180382	148181555	+	SAMDS	0x0
4901	chr6	148864652	148865751	+	SASH1	0x1
4902	chr6	149114303	149115527	+	UST	0x0
4903	chr6	149373105	149374324	−	UST	0x0
4904	chr6	149731584	149732938	−	TAB2	0x0
4905	chr6	149771073	149772242	−	ZC3H12D	0x0
4906	chr6	149887280	149888487	+	C6orf72	0x0
4907	chr6	150070386	150071604	+	PCMT1	0x0
4908	chr6	150131824	150133021	+	PCMT1	0x0
4909	chr6	151007810	151008958	+	PLEKHG1	0x0
4910	chr6	151230797	151231991	−	MTHFD1L	0x0
4911	chr6	151715338	151716552	+	AKAP12	0x1
4912	chr6	153602990	153604390	−	RGS17	0x0
4913	chr6	153741015	153742253	+	OPRM1	0x0
4914	chr6	154510891	154512064	+	OPRM1	0x0
4915	chr6	157099272	157100482	+	ARID1B	0x2
4916	chr6	157297408	157298585	+	ARID1B	0x2
4917	chr6	158501709	158502885	+	SYNJ2	0x0
4918	chr6	158732582	158734565	+	TULP4	0x0
4919	chr6	158836738	158837951	+	TULP4	0x0
4920	chr6	159005798	159006993	+	TMEM181	0x0
4921	chr6	159010147	159011345	+	TMEM181	0x0
4922	chr6	159222196	159223361	−	EZR	0x2
4923	chr6	160100679	160101871	−	SOD2	0x1
4924	chr6	160147489	160148641	−	LOC100129518	0x0
4925	chr6	160199235	160200470	−	TCP1	0x0
4926	chr6	160200704	160201944	−	SNORA20	0x0
4927	chr6	160200704	160201944	−	TCP1	0x0
4928	chr6	161574255	161575389	−	AGPAT4	0x0
4929	chr6	161693681	161694857	−	AGPAT4	0x0
4930	chr6	163729635	163730813	−	LOC285796	0x0
4931	chr6	163992894	163994954	+	QKI	0x0
4932	chr6	167096615	167097792	−	RPS6KA2	0x1
4933	chr6	167232349	167233545	−	RPS6KA2	0x1
4934	chr6	167431288	167432414	+	FGFR1OP	0x2
4935	chr6	169717516	169718713	−	THBS2	0x0
4936	chr6	169959010	169960179	−	WDR27	0x0
4937	chr6	170063733	170065042	−	WDR27	0x0
4938	chr6	170107201	170108322	−	PHF10	0x0
4939	chr6	170108331	170109430	−	PHF10	0x0
4940	chr6	170109684	170110800	−	PHF10	0x0
4941	chr6	170715138	170716380	−	FAM120B	0x0
4942	chr6	170793708	170794808	−	TBP	0x0
4943	chr7	716322	717533	−	PRKAR1B	0x0
4944	chr7	793397	794759	−	HEATR2	0x0
4945	chr7	882031	883164	+	SUN1	0x0
4946	chr7	1114643	1115856	−	C7orf50	0x0
4947	chr7	1148073	1149265	−	C7or(50	0x0
4948	chr7	2209517	2210716	−	MAD1L1	0x1
4949	chr7	2335042	2336261	−	SNX8	0x0
4950	chr7	2419510	2420742	+	EIF3B	0x0
4951	chr7	2653169	2654343	+	IQCE	0x0
4952	chr7	2702439	2704021	+	TTYH3	0x0
4953	chr7	2762696	2763886	−	GNA12	0x0
4954	chr7	2765610	2766723	−	GNA12	0x0
4955	chr7	3038321	3039532	+	AMZ1	0x0
4956	chr7	3152398	3153597	−	CARD11	0x2
4957	chr7	3297158	3298337	−	CARD11	0x2
4958	chr7	3347392	3348543	+	SDK1	0x0
4959	chr7	3613078	3614275	+	SDK1	0x0
4960	chr7	3998820	4000014	+	SDK1	0x0
4961	chr7	4118598	4119714	+	SDK1	0x0
4962	chr7	5253679	5254827	+	WIPI2	0x0
4963	chr7	5269929	5271252	+	WIPI2	0x0
4964	chr7	5347601	5348689	−	TNRC18	0x0
4965	chr7	5351989	5353124	−	TNRC18	0x0
4966	chr7	5395880	5397015	−	TNRC18	0x0
4967	chr7	5433553	5434723	−	TNRC18	0x0
4968	chr7	5450755	5451944	−	TNRC18	0x0
4969	chr7	5536480	5537661	−	MIR589	0x0
4970	chr7	5540860	5542057	−	FBXL18	0x0
4971	chr7	5566668	5567958	−	ACTB	0x2
4972	chr7	5685864	5687035	−	RNF216	0x0
4973	chr7	6025876	6027098	−	PMS2	0x1
4974	chr7	6098042	6099244	−	EIF2AK1	0x0
4975	chr7	6380025	6381233	−	C7orf70	0x0
4976	chr7	6441838	6444007	+	RAC1	0x0
4977	chr7	6500568	6501811	−	KDELR2	0x0
4978	chr7	7882404	7883601	+	LOC729852	0x0
4979	chr7	8112486	8113702	+	GLCCI1	0x0
4980	chr7	8127283	8128479	+	GLCCI1	0x0
4981	chr7	11137465	11138681	+	PHF14	0x0
4982	chr7	12024744	12025924	−	THSD7A	0x0
4983	chr7	12915824	12917060	+	ARL4A	0x0
4984	chr7	15781909	15783031	−	LOC100506025	0x0
4985	chr7	16739862	16741056	−	BZW2	0x0
4986	chr7	16823462	16824630	+	TSPAN13	0x0
4987	chr7	22895658	22896857	+	SNORD93	0x0
4988	chr7	23224278	23225503	+	NUPL2	0x0
4989	chr7	23239252	23240488	−	NUPL2	0x0
4990	chr7	23446198	23447358	−	IGF2BP3	0x0
4991	chr7	23530465	23531648	+	RPS2P32	0x0
4992	chr7	24731533	24732682	+	MPP6	0x0
4993	chr7	25988340	25989530	−	MIR148A	0x0
4994	chr7	26230917	26232469	−	HNRNPA2B1	0x2
4995	chr7	26236459	26237797	−	HNRNPA2B1	0x2
4996	chr7	26239671	26241083	−	HNRNPA2B1	0x2
4997	chr7	26241519	26242615	+	CBX3	0x0
4998	chr7	26364063	26365261	+	SNX10	0x0
4999	chr7	26706811	26708082	−	SKAP2	0x0
5000	chr7	27202973	27204085	−	HOXA10-HOXA9	0x0
5001	chr7	27202973	27204085	−	HOXA9	0x2
5002	chr7	27205067	27206183	−	HOXA9	0x2
5003	chr7	28081190	28082374	−	JAZF1	0x2
5004	chr7	28179077	28180280	−	JAZF1	0x2
5005	chr7	28832876	28834100	+	CREB5	0x0
5006	chr7	28843490	28844709	+	CREB5	0x0
5007	chr7	29960439	29961649	−	SCRN1	0x0
5008	chr7	30199055	30200368	+	C7orf41	0x0
5009	chr7	30201709	30202892	+	C7or(41	0x0
5010	chr7	30401633	30402869	+	ZNRF2	0x0
5011	chr7	32602085	32603255	+	AVL9	0x0
5012	chr7	32768061	32769271	+	ZNRF2P1	0x0
5013	chr7	34970565	34971769	−	DPY19L1	0x0
5014	chr7	35187334	35188527	−	DPY19L2P1	0x0
5015	chr7	35943851	35945050	+	SEPT7	0x0
5016	chr7	37474190	37475366	+	GPR141	0x0
5017	chr7	38764683	38766032	−	VPS41	0x0
5018	chr7	38767749	38768941	−	VPS41	0x0
5019	chr7	40046956	40048149	+	CDK13	0x0
5020	chr7	40122300	40123482	+	CDK13	0x0
5021	chr7	40716495	40717647	+	C7orf10	0x0
5022	chr7	43664776	43665987	−	C7orf44	0x0
5023	chr7	43676994	43678133	−	C7orf44	0x0
5024	chr7	43688077	43689239	−	C7orf44	0x0
5025	chr7	43755954	43757114	−	C7orf44	0x0
5026	chr7	44017403	44018614	−	POLR2J4	0x0
5027	chr7	44156210	44157388	−	POLD2	0x0
5028	chr7	44252240	44253901	+	YKT6	0x0
5029	chr7	44422977	44425078	−	NUDCD3	0x0
5030	chr7	44506929	44508226	+	OGDH	0x0
5031	chr7	44615133	44616293	−	DDX56	0x0
5032	chr7	44867630	44869296	−	H2AFV	0x0
5033	chr7	44869491	44870653	−	H2AFV	0x0
5034	chr7	44871384	44872476	−	H2AFV	0x0
5035	chr7	45024431	45025655	−	SNHG15	0x0
5036	chr7	45024431	45025655	−	SNORA9	0x0
5037	chr7	45055716	45056839	+	CCM2	0x0
5038	chr7	45143432	45145126	−	SNORA5A	0x0
5039	chr7	45143432	45145126	−	SNORA5C	0x0
5040	chr7	45143432	45145126	−	TBRG4	0x0
5041	chr7	45631850	45633046	+	ADCY1	0x2
5042	chr7	45687751	45688961	+	ADCY1	0x2
5043	chr7	47883015	47884214	−	PKD1L1	0x0
5044	chr7	48329866	48330965	+	ABCA13	0x0
5045	chr7	51125959	51127160	−	COBL	0x0
5046	chr7	51140419	51141571	+	COBL	0x0
5047	chr7	53573745	53575001	+	POM121L12	0x0
5048	chr7	53843321	53844539	+	POM121L12	0x0
5049	chr7	55712928	55714027	+	LANCL2	0x0
5050	chr7	55992166	55993377	+	ZNF713	0x0
5051	chr7	56047818	56048984	+	GBAS	0x0
5052	chr7	56050957	56052136	+	GBAS	0x0
5053	chr7	56066418	56067572	+	GBAS	0x0
5054	chr7	56111114	56112302	−	PSPH	0x0
5055	chr7	56122829	56124002	+	CCT6A	0x0
5056	chr7	56125566	56126665	+	CCT6A	0x0
5057	chr7	56130833	56132038	+	CCT6A	0x0
5058	chr7	56130833	56132038	+	SUMF2	0x0
5059	chr7	56168775	56169951	−	CHCHD2	0x0
5060	chr7	63806388	63807524	+	ZNF736	0x0
5061	chr7	64512487	64513689	+	CCT6P3	0x0
5062	chr7	65220022	65221173	+	CCT6P1	0x0
5063	chr7	65220022	65221173	+	SNORA22	0x0
5064	chr7	66444580	66445777	+	TYW1	0x0
5065	chr7	66452731	66453910	−	SBDS	0x2
5066	chr7	66461505	66462727	+	TYW1	0x0
5067	chr7	66696321	66697506	−	PMS2P4	0x0
5068	chr7	66732088	66733253	−	PMS2P4	0x0
5069	chr7	68526830	68528282	+	AUTS2	0x0
5070	chr7	69137623	69139895	+	AUTS2	0x0
5071	chr7	69150855	69152052	+	AUTS2	0x0
5072	chr7	69890680	69891884	+	AUTS2	0x0
5073	chr7	69944884	69946122	+	AUTS2	0x0
5074	chr7	70095006	70096231	+	AUTS2	0x0
5075	chr7	70158630	70159729	+	AUTS2	0x0
5076	chr7	70162406	70163506	+	AUTS2	0x0
5077	chr7	70228678	70229863	+	AUTS2	0x0
5078	chr7	72210226	72211362	−	TYW1B	0x0
5079	chr7	72384475	72385573	+	POM 121	0x0
5080	chr7	72855521	72856620	−	BAZ1B	0x0
5081	chr7	72892223	72893442	−	BAZ1B	0x0
5082	chr7	73028896	73030065	−	MLXIPL	0x0
5083	chr7	73609735	73611412	+	EIF4H	0x0
5084	chr7	74011007	74012204	+	GTF21RD1	0x0
5085	chr7	75013767	75014967	+	TRIM73	0x0
5086	chr7	75013767	75014967	+	TRIM74	0x0
5087	chr7	75616282	75617424	−	TMEM120A	0x0
5088	chr7	75677085	75678284	+	MDH2	0x0
5089	chr7	75695075	75696451	+	MDH2	0x0
5090	chr7	76183802	76184974	+	LOC100133091	0x0
5091	chr7	77288076	77289291	+	PTPN12	0x1
5092	chr7	77325584	77329262	+	RSBN1L	0x0
5093	chr7	77409754	77411102	+	RSBN1L	0x0
5094	chr7	77444662	77445817	+	PHTF2	0x0
5095	chr7	77819775	77820999	+	RPL13AP17	0x0
5096	chr7	84217800	84218994	−	SEMA3A	0x0
5097	chr7	85957572	85958791	+	GRM3	0x2
5098	chr7	91745871	91747042	−	CYP51A1	0x0
5099	chr7	92121693	92122871	−	PEX1	0x0
5100	chr7	94259800	94260938	−	SGCE	0x4
5101	chr7	94277985	94279186	−	SGCE	0x4
5102	chr7	95182157	95183355	+	ASB4	0x4
5103	chr7	97500925	97502164	−	ASNS	0x0
5104	chr7	97822980	97824146	+	LMTK2	0x0
5105	chr7	98571475	98572623	+	TRRAP	0x2
5106	chr7	98580407	98581636	+	TRRAP	0x2
5107	chr7	99040246	99041345	−	CPSF4	0x0
5108	chr7	99055334	99056509	−	ATP5J2	0x0
5109	chr7	99063102	99064286	−	ATP5J2	0x0
5110	chr7	99063102	99064286	−	ATP5J2-PTCD1	0x0
5111	chr7	99070753	99071852	+	ZNF789	0x0
5112	chr7	99090314	99091491	−	ZNF394	0x0
5113	chr7	99164579	99165769	+	ZNF655	0x0
5114	chr7	99620568	99621775	+	ZKSCAN1	0x0
5115	chr7	99696493	99697583	−	MCM7	0x0
5116	chr7	99766778	99767983	−	GPC2	0x0
5117	chr7	100027125	100028311	+	MEPCE	0x0
5118	chr7	100171876	100172981	−	LRCH4	0x0
5119	chr7	100177762	100178920	−	LRCH4	0x0
5120	chr7	100880641	100881974	−	CLDN15	0x0
5121	chr7	100895195	100896397	+	ZNHIT1	0x0
5122	chr7	101518509	101519697	−	CUX1	0x2
5123	chr7	101614007	101615204	+	CUX1	0x2
5124	chr7	101870302	101871497	+	CUX1	0x2
5125	chr7	102090409	102091726	+	ORAI2	0x0
5126	chr7	102103915	102105079	−	ALKBH4	0x0
5127	chr7	102273284	102274466	−	POLR2J2	0x0
5128	chr7	102776284	102777472	−	RPL19P12	0x0
5129	chr7	102956740	102957866	−	DNAJC2	0x0
5130	chr7	102959728	102960926	−	DNAJC2	0x0
5131	chr7	102987648	102988747	+	PSMC2	0x0
5132	chr7	103017293	103018395	+	PSMC2	0x0
5133	chr7	104183926	104185102	−	LOC645591	0x0
5134	chr7	104989419	104990519	−	SRPK2	0x0
5135	chr7	105130826	105131959	−	PUS7	0x0
5136	chr7	105730920	105732237	−	SYPL1	0x0
5137	chr7	106966970	106968196	−	COG5	0x0
5138	chr7	107392326	107393492	+	CBLL1	0x0
5139	chr7	107579969	107581118	−	LAMB1	0x0
5140	chr7	107604477	107605657	−	LAMB1	0x0
5141	chr7	107641647	107642890	−	LAMB1	0x0
5142	chr7	107788055	107789246	−	NRCAM	0x1
5143	chr7	109647779	109648956	−	EIF3IP1	0x0
5144	chr7	111928314	111929569	+	ZNF277	0x0
5145	chr7	112094112	112095341	+	IFRD1	0x0
5146	chr7	113813661	113814849	+	FOXP2	0x0
5147	chr7	113873613	113874725	+	FOXP2	0x0
5148	chr7	116655877	116657135	+	ST7-OT4	0x0
5149	chr7	116864291	116865488	−	ST7	0x1
5150	chr7	121022060	121023221	−	FAM3C	0x0
5151	chr7	123181470	123182631	−	NDUFA5	0x0
5152	chr7	126826996	126828167	−	GRM8	0x2
5153	chr7	127002369	127003478	−	ZNF800	0x0
5154	chr7	127011169	127012346	−	ZNF800	0x0
5155	chr7	127292221	127293424	+	SND1	0x0
5156	chr7	127304238	127305368	−	SND1	0x0
5157	chr7	127717944	127719181	−	SND1	0x0
5158	chr7	128045356	128046535	−	IMPDH1	0x0
5159	chr7	128144617	128145843	−	METTL2B	0x0
5160	chr7	128268899	128270067	+	FU45340	0x0
5161	chr7	128294201	128295432	+	FU4S340	0x0
5162	chr7	128336957	128338351	+	FAM71F2	0x0
5163	chr7	128410338	128411503	+	CALU	0x0
5164	chr7	128626267	128627427	−	TNPO3	0x0
5165	chr7	128804197	128805297	+	TSPAN33	0x0
5166	chr7	128828291	128829490	+	SMO	0x1
5167	chr7	128844598	128846620	+	SMO	0x1
5168	chr7	128956910	128958109	+	AHCYL2	0x0
5169	chr7	129249052	129250217	−	MIR182	0x0
5170	chr7	129771754	129772914	+	KLHDC10	0x0
5171	chr7	132719105	132721265	−	CHCHD3	0x0
5172	chr7	134126762	134127961	−	AKR1B1	0x1
5173	chr7	134446424	134447609	−	AKR1B1	0x1
5174	chr7	134653877	134655027	+	CALD1	0x0
5175	chr7	135262978	135264232	+	NUP205	0x0
5176	chr7	135299192	135300395	−	NUP205	0x0
5177	chr7	135564469	135565613	−	LUZP6	0x0
5178	chr7	135564469	135565613	−	MTPN	0x0
5179	chr7	135612497	135613615	−	LUZP6	0x0
5180	chr7	135612497	135613615	−	MTPN	0x0
5181	chr7	135631923	135633117	−	LUZP6	0x0
5182	chr7	135631923	135633117	−	MTPN	0x0
5183	chr7	137561561	137562688	−	CREB3L2	0x2
5184	chr7	137593795	137594957	−	CREB3L2	0x2
5185	chr7	137641335	137642504	−	CREB3L2	0x2
5186	chr7	138229348	138230509	+	TRIM24	0x1
5187	chr7	138601353	138602530	−	KIAA1549	0x0
5188	chr7	138708377	138709573	−	ZC3HAV1L	0x0
5189	chr7	139060142	139061336	+	LUC7L2	0x0
5190	chr7	139091472	139092571	+	LUC7L2	0x0
5191	chr7	139163207	139164420	−	KLRG2	0x0
5192	chr7	139252540	139254304	−	HIPK2	0x1
5193	chr7	139255381	139257357	−	HIPK2	0x1
5194	chr7	139415555	139417089	−	HIPK2	0x1
5195	chr7	139991958	139993146	−	SLC37A3	0x0
5196	chr7	140578969	140580149	−	BRAF	0x2
5197	chr7	140608227	140609407	−	BRAF	0x2
5198	chr7	140949281	140950478	+	LOC100507421	0x0
5199	chr7	140989729	140990945	+	LOC100507421	0x0
5200	chr7	141427256	141428517	−	WEE2	0x0
5201	chr7	142828739	142829949	−	OR6W1P	0x0
5202	chr7	148517064	148518265	−	EZH2	0x2
5203	chr7	148637989	148639256	+	CUL1	0x1
5204	chr7	148683652	148684931	−	PDIA4	0x2
5205	chr7	148815628	148816762	−	ZNF425	0x0
5206	chr7	148822219	148823398	−	ZNF425	0x0
5207	chr7	148875639	148876808	+	ZNF398	0x0
5208	chr7	149187521	149188679	−	ZNF746	0x0
5209	chr7	149281240	149282410	+	KRBA1	0x0
5210	chr7	149361344	149362611	+	KRBA1	0x0
5211	chr7	149387704	149388911	−	ZNF767	0x0
5212	chr7	149411854	149413217	+	KRBA1	0x0
5213	chr7	149575886	149577679	+	ATP6V0E2	0x0
5214	chr7	150070282	150071455	+	REPIN1	0x0
5215	chr7	150815954	150817053	+	AGAP3	0x0
5216	chr7	150910175	150911551	−	ABCF2	0x0
5217	chr7	150967839	150969008	−	SMARCD3	0x0
5218	chr7	151215094	151216312	−	RHEB	0x0
5219	chr7	151921067	151922240	−	MLL3	0x2
5220	chr7	152097427	152098632	−	MLL3	0x2
5221	chr7	155099915	155101047	+	INSIG1	0x0
5222	chr7	155250236	155251340	+	EN2	0x0
5223	chr7	155572294	155573527	+	RBM33	0x0
5224	chr7	156473215	156474319	−	LMBR1	0x0
5225	chr7	157131140	157132337	+	DNAJB6	0x0
5226	chr7	157207302	157208421	+	DNAJB6	0x0
5227	chr7	158482226	158483355	−	NCAPG2	0x0
5228	chr7	158523818	158524891	−	ESYT2	0x0
5229	chr7	158526068	158527207	−	ESYT2	0x0
5230	chr8	171812	172992	−	RPL23AP53	0x0
5231	chr8	650437	651644	−	ERICH1	0x0
5232	chr8	1728071	1729269	+	CLN8	0x2
5233	chr8	1851872	1853143	+	ARHGEF10	0x2
5234	chr8	1892421	1893656	+	ARHGEF10	0x2
5235	chr8	8719116	8720272	−	MFHAS1	0x1
5236	chr8	9522657	9523873	+	TNKS	0x0
5237	chr8	10543587	10544750	+	C8orf74	0x0
5238	chr8	10553225	10554430	−	SOX7	0x1
5239	chr8	10989659	10990816	−	XKR6	0x0
5240	chr8	11018991	11020365	−	XKR6	0x0
5241	chr8	11179720	11180920	+	MTMR9	0x0
5242	chr8	14088163	14089374	−	SGCZ	0x0
5243	chr8	14466831	14468007	−	SGCZ	0x0
5244	chr8	15608483	15609698	+	TUSC3	0x1
5245	chr8	16969800	16970982	+	EFHA2	0x0
5246	chr8	16973468	16974591	+	EFHA2	0x0
5247	chr8	17020725	17021901	+	ZDHHC2	0x1
5248	chr8	17528806	17529982	−	MTUS1	0x1
5249	chr8	17600589	17601753	−	MTUS1	0x1
5250	chr8	21783081	21784262	+	XPO7	0x2
5251	chr8	22273079	22274302	+	SLC39A14	0x0
5252	chr8	22278525	22279701	+	SLC39A14	0x0
5253	chr8	22993341	22994750	−	TNFRSF10D	0x0
5254	chr8	23001245	23002452	−	TNFRSF10D	0x0
5255	chr8	23118432	23119876	+	CHMP7	0x0
5256	chr8	23933949	23935207	−	STC1	0x2
5257	chr8	26466443	26467884	+	DPYSL2	0x0
5258	chr8	26513085	26514287	+	DPYSL2	0x0
5259	chr8	27626561	27627757	−	CCDC25	0x0
5260	chr8	27642609	27643794	+	ESCO2	0x0
5261	chr8	27661194	27662353	+	ESCO2	0x0
5262	chr8	28610258	28611360	+	EXTL3	0x1
5263	chr8	28925365	28926640	−	K1F13B	0x0
5264	chr8	28973920	28975219	−	KIF13B	0x0
5265	chr8	29191850	29193027	−	DUSP4	0x0
5266	chr8	29926842	29927959	−	TMEM66	0x0
5267	chr8	30535411	30536703	−	GSR	0x0
5268	chr8	30918443	30919643	+	WRN	0x2
5269	chr8	30941596	30942794	+	WRN	0x2
5270	chr8	30973889	30975103	+	WRN	0x2
5271	chr8	33307984	33309159	−	FUT10	0x0
5272	chr8	33370435	33371696	+	MAK16	0x0
5273	chr8	33405399	33406500	−	RNF122	0x0
5274	chr8	37351279	37352488	−	LOC728024	0x0
5275	chr8	37548760	37549962	−	LOC728024	0x0
5276	chr8	37555657	37556832	+	ZNF703	0x0
5277	chr8	37610997	37612138	+	ERLIN2	0x0
5278	chr8	37734373	37735537	−	RAB11FIP1	0x0
5279	chr8	37896767	37897965	+	EIF4EBP1	0x0
5280	chr8	37964730	37965937	+	ASH2L	0x0
5281	chr8	38238788	38240521	−	WHSC1L1	0x1
5282	chr8	41789279	41790380	−	KAT6A	0x2
5283	chr8	42069466	42070659	+	AP3M2	0x0
5284	chr8	42751527	42752702	−	RNF170	0x0
5285	chr8	48454145	48455421	+	KIAA0146	0x0
5286	chr8	48690474	48691581	−	PRKDC	0x0
5287	chr8	48719526	48720712	−	PRKDC	0x0
5288	chr8	56698693	56699907	+	TGS1	0x0
5289	chr8	56702837	56704080	+	TGS1	0x0
5290	chr8	56792545	56793692	+	LYN	0x0
5291	chr8	56986406	56987620	−	RPS20	0x0
5292	chr8	56986406	56987620	−	SNORD54	0x0
5293	chr8	59361453	59362789	+	UBXN2B	0x0
5294	chr8	59495823	59497028	−	NSMAF	0x0
5295	chr8	60367861	60369092	+	SDCBP	0x0
5296	chr8	61141149	61142305	−	CAS	0x0
5297	chr8	61380988	61382139	−	CA8	0x0
5298	chr8	61428976	61430164	+	RAB2A	0x0
5299	chr8	62558694	62559890	−	ASPH	0x0
5300	chr8	65062889	65064025	−	LOC401463	0x0
5301	chr8	67025014	67026251	+	DNAJC5B	0x0
5302	chr8	67834131	67835343	−	SNHG6	0x0
5303	chr8	67834131	67835343	−	SNORD87	0x0
5304	chr8	67854441	67855579	−	TCF24	0x0
5305	chr8	69218262	69219475	+	C8orf34	0x0
5306	chr8	69628958	69630158	+	C8orf34	0x0
5307	chr8	70601758	70603154	−	SLC05A1	0x0
5308	chr8	71015648	71016846	−	NCOA2	0x2
5309	chr8	71485199	71486420	−	TRAM1	0x0
5310	chr8	72549549	72550725	−	MSC	0x0
5311	chr8	73557323	73558542	+	KCNB2	0x0
5312	chr8	74558696	74559805	−	STAU2	0x0
5313	chr8	77776192	77777558	+	ZFHX4	0x2
5314	chr8	80676493	80677670	−	HEY1	0x2
5315	chr8	80708218	80709377	+	STMN2	0x0
5316	chr8	81039463	81040687	−	TPD52	0x0
5317	chr8	84510943	84512141	−	C8orf59	0x0
5318	chr8	86191435	86192537	+	CAB	0x0
5319	chr8	87528903	87530098	+	CPNE3	0x0
5320	chr8	95406717	95407924	−	RAD54B	0x0
5321	chr8	95854520	95855619	+	INTS8	0x0
5322	chr8	98672727	98573911	+	MTDH	0x0
5323	chr8	98817057	98818222	+	LAPTM4B	0x0
5324	chr8	98827727	98828903	+	LAPTM4B	0x0
5325	chr8	101485556	101486759	−	ANKRD46	0x0
5326	chr8	101714872	101716041	−	PABPC1	0x2
5327	chr8	101724361	101725581	−	PABPC1	0x2
5328	chr8	101727184	101728357	−	PABPC1	0x2
5329	chr8	101729540	101730664	−	PABPC1	0x2
5330	chr8	101733058	101734450	−	PABPC1	0x2
5331	chr8	102149814	102150984	+	FU42969	0x0
5332	chr8	103423528	103424664	−	UBR5	0x2
5333	chr8	103845897	103847028	−	AZIN1	0x0
5334	chr8	106914349	106915532	−	ABRA	0x0
5335	chr8	107709298	107710494	−	ABRA	0x0
5336	chr8	110281595	110282791	−	NUDCD1	0x0
5337	chr8	110353471	110354647	+	ENY2	0x0
5338	chr8	116563419	116564599	−	TRPS1	0x0
5339	chr8	119396638	119397854	−	SAMD12	0x0
5340	chr8	120743496	120744716	−	TAF2	0x2
5341	chr8	120874372	120875604	+	DEPTOR	0x0
5342	chr8	121501990	121503167	+	MTBP	0x0
5343	chr8	124025136	124026313	−	DERL1	0x0
5344	chr8	124053823	124055003	−	DERL1	0x0
5345	chr8	124095937	124097121	+	WDR67	0x0
5346	chr8	124250286	124251573	−	C8orf76	0x0
5347	chr8	124250286	124251573	−	ZHX1-C8ORF76	0x0
5348	chr8	124511119	124512309	−	FBXO32	0x1
5349	chr8	124826019	124827118	+	FAM91A1	0x0
5350	chr8	125503049	125504257	+	RNF139	0x0
5351	chr8	126257758	126258960	+	NSMCE2	0x0
5352	chr8	126467614	126468814	+	TRIB1	0x2
5353	chr8	126584427	126585626	+	TRIB1	0x2
5354	chr8	128752709	128753881	+	MYC	0x2
5355	chr8	128878369	128879800	+	PVT1	0x0
5356	chr8	128902427	128903666	+	PVT1	0x0
5357	chr8	129006031	129007240	+	PVT1	0x0
5358	chr8	129232188	129233396	+	MIR1208	0x0
5359	chr8	131369782	131370944	−	ASAP1	0x0
5360	chr8	134249222	134250405	−	NDRG1	0x1
5361	chr8	135602264	135603445	−	ZFAT	0x4
5362	chr8	136484515	136485664	+	KHDRBS3	0x0
5363	chr8	141539629	141540966	−	EIF2C2	0x0
5364	chr8	141706964	141708108	−	PTK2	0x0
5365	chr8	144390951	144392074	−	TOP1MT	0x0
5366	chr8	144589736	144590895	−	ZC3H3	0x0
5367	chr8	144623760	144624957	+	GSDMD	0x0
5368	chr8	144656550	144657716	−	NAPRT1	0x0
5369	chr8	144665432	144666631	−	EEF1D	0x0
5370	chr8	144668416	144669512	−	EEF1D	0x0
5371	chr8	144671344	144672503	−	EEF1D	0x0
5372	chr8	144872867	144874212	−	SCRIB	0x1
5373	chr8	144995170	144996345	−	PLEC	0x0
5374	chr8	144996673	144997860	−	PLEC	0x0
5375	chr8	145512299	145513597	−	BOP1	0x0
5376	chr8	145514906	145516064	+	HSF1	0x0
5377	chr8	145735164	145736323	+	MFSD3	0x0
5378	chr8	145975673	145976844	−	ZNF251	0x0
5379	chr8	146014646	146015821	−	RPL8	0x0
5380	chr8	146016941	146018035	−	RPL8	0x0
5381	chr9	579222	580422	+	KANK1	0x1
5382	chr9	583912	585146	+	KANK1	0x1
5383	chr9	2358753	2359971	−	SMARCA2	0x1
5384	chr9	3214212	3215432	−	KCNV2	0x0
5385	chr9	3508378	3509541	−	RFX3	0x0
5386	chr9	4826335	4827507	+	RCL1	0x0
5387	chr9	4833549	4834747	−	RCL1	0x0
5388	chr9	5734043	5735202	+	KIAA1432	0x0
5389	chr9	9441508	9442749	−	KDM4C	0x0
5390	chr9	13124573	13125772	−	MPDZ	0x0
5391	chr9	14611622	14612784	−	ZDHHC21	0x0
5392	chr9	14640065	14641279	−	ZDHHC21	0x0
5393	chr9	14921661	14922812	−	FREM1	0x0
5394	chr9	15482841	15484138	−	PSIP1	0x2
5395	chr9	15505342	15506551	−	PSIP1	0x2
5396	chr9	16828016	16829203	−	BNC2	0x0
5397	chr9	17413189	17414414	−	CNTLN	0x0
5398	chr9	17440398	17441554	−	BNC2	0x0
5399	chr9	19055113	19056309	−	HAUS6	0x0
5400	chr9	19063173	19064362	−	HAUS6	0x0
5401	chr9	19063173	19064362	−	SCARNA8	0x0
5402	chr9	19372260	19373473	+	DENNO4C	0x0
5403	chr9	19375853	19377070	−	RPS6	0x0
5404	chr9	19377873	19380410	−	RPS6	0x0
5405	chr9	19383288	19384499	+	DENND4C	0x0
5406	chr9	20429737	20430924	−	MLLT3	0x2
5407	chr9	20548245	20549446	−	MIR4474	0x0
5408	chr9	20786340	20787535	+	KIAA1797	0x0
5409	chr9	20810807	20811984	−	MLLT3	0x2
5410	chr9	20896813	20898020	+	KIAA1797	0x0
5411	chr9	20923117	20924315	+	KIAA1797	0x0
5412	chr9	21332177	21333335	−	KLHL9	0x0
5413	chr9	21698742	21700024	+	MTAP	0x1
5414	chr9	21861943	21863042	+	MTAP	0x1
5415	chr9	21867924	21869151	+	MTAP	0x1
5416	chr9	21903931	21905084	+	MTAP	0x1
5417	chr9	22081029	22082228	+	CDKN2B-AS1	0x0
5418	chr9	25676769	25677898	−	TUSC1	0x0
5419	chr9	26658888	26660011	+	IFT74	0x0
5420	chr9	26935048	26936169	−	PLAA	0x0
5421	chr9	28707158	28708331	−	LINGO2	0x0
5422	chr9	28846936	28848152	−	MIR876	0x0
5423	chr9	33011499	33012677	−	APTX	0x0
5424	chr9	33023893	33025172	−	SMU1	0x0
5425	chr9	33038376	33039941	+	DNAJA1	0x0
5426	chr9	33318207	33319380	+	NFX1	0x0
5427	chr9	33916595	33917697	+	UBE2R2	0x0
5428	chr9	33952273	33953373	−	SNORD121A	0x0
5429	chr9	33952273	33953373	−	UBAP2	0x0
5430	chr9	33955557	33956731	−	UBAP2	0x0
5431	chr9	33960256	33961456	−	UBAP2	0x0
5432	chr9	33963170	33964252	−	UBAP2	0x0
5433	chr9	34011964	34013151	−	UBAP2	0x0
5434	chr9	34016524	34017695	−	UBAP2	0x0
5435	chr9	34049409	34050630	−	SNORD121B	0x0
5436	chr9	34087271	34088491	−	DCAF12	0x0
5437	chr9	34185383	34186545	−	UBAP1	0x0
5438	chr9	34282012	34283214	−	KIF24	0x0
5439	chr9	34634177	34635546	−	SIGMAR1	0x0
5440	chr9	35101379	35102543	−	STOML2	0x0
5441	chr9	35398409	35399768	+	UNC13B	0x0
5442	chr9	35547214	35548291	+	RUSC2	0x0
5443	chr9	35657197	35658583	−	RMRP	0x0
5444	chr9	35705464	35707665	−	TLN1	0x2
5445	chr9	35712376	35713551	−	TLN1	0x2
5446	chr9	35737757	35738923	−	GBA2	0x0
5447	chr9	35748405	35749597	−	GBA2	0x0
5448	chr9	36211270	36212469	−	CLTA	0x0
5449	chr9	36215412	36216592	−	GNE	0x0
5450	chr9	37161890	37162980	+	ZCCHC7	0x0
5451	chr9	37180719	37181818	−	ZCCHC7	0x0
5452	chr9	37394697	37395893	+	GRHPR	0x0
5453	chr9	37425972	37427149	+	GRHPR	0x0
5454	chr9	37757009	37758131	+	RG9MTD3	0x0
5455	chr9	37776759	37777892	−	EXOSC3	0x0
5456	chr9	38392326	38393556	+	ALDH1B1	0x0
5457	chr9	38406249	38407526	−	IGFBPL1	0x1
5458	chr9	38408287	38409466	−	IGFBPL1	0x1
5459	chr9	38542057	38543182	−	ANKRD18A	0x0
5460	chr9	38548716	38549888	−	ANKRD18A	0x0
5461	chr9	45454163	45455328	+	FAM27A	0x0
5462	chr9	66862489	66863606	−	LOC286297	0x0
5463	chr9	72276359	72277573	−	APBA1	0x4
5464	chr9	72802958	72804155	−	LOC100507244	0x0
5465	chr9	74319441	74320649	−	TMEM2	0x0
5466	chr9	77639260	77640400	−	C9orf41	0x0
5467	chr9	79000589	79001744	−	RFK	0x0
5468	chr9	79186185	79187441	+	GCNT1	0x0
5469	chr9	80333954	80335131	−	GNAQ	0x2
5470	chr9	80461575	80462760	−	GNAQ	0x2
5471	chr9	80526971	80528160	−	GNAQ	0x2
5472	chr9	80624392	80625619	−	GNAQ	0x2
5473	chr9	81149233	81150432	+	PSAT1	0x0
5474	chr9	82201319	82202535	+	TIE4	0x2
5475	chr9	84036070	84037267	+	FAM75D5	0x0
5476	chr9	84250539	84251853	−	TLE1	0x0
5477	chr9	84486792	84487991	−	TLE1	0x0
5478	chr9	85827443	85828601	−	FRMD3	0x0
5479	chr9	86186741	86188057	−	FRMD3	0x0
5480	chr9	86292867	86294079	−	UBQIN1	0x0
5481	chr9	86582599	86583805	−	HNRNPK	0x0
5482	chr9	86598602	86599787	+	RMI1	0x0
5483	chr9	88260737	88261915	−	AGTPBP1	0x0
5484	chr9	88307117	88308237	−	AGTPBP1	0x0
5485	chr9	90115188	90116387	+	DAPK1	0x1
5486	chr9	91925658	91926817	+	CKS2	0x0
5487	chr9	94053627	94054823	−	AUH	0x0
5488	chr9	94666775	94667954	−	ROR2	0x0
5489	chr9	95017779	95019585	−	IARS	0x0
5490	chr9	95026780	95027945	−	IARS	0x0
5491	chr9	95148146	95149332	+	CENPP	0x0
5492	chr9	95289868	95290971	+	CENPP	0x0
5493	chr9	96054324	96055449	+	WNK2	0x1
5494	chr9	96259226	96260410	+	FAM120A	0x1
5495	chr9	96260521	96261610	+	FAM120A	0x1
5496	chr9	96304540	96306154	+	FAM120A	0x1
5497	chr9	96425818	96426994	+	PHF2	0x0
5498	chr9	97626912	97628116	+	MIR2278	0x0
5499	chr9	97747161	97748371	+	C9orf3	0x0
5500	chr9	98205195	98206341	−	PTCH1	0x1
5501	chr9	98665745	98667943	+	C9orf102	0x0
5502	chr9	98703213	98704414	+	C9orf102	0x0
5503	chr9	98864832	98866024	−	LOC158434	0x0
5504	chr9	99541077	99542255	−	ZNF510	0x0
5505	chr9	100434963	100436183	+	NCBP1	0x0
5506	chr9	100443119	100444445	+	NCBP1	0x0
5507	chr9	100777282	100778579	+	ANP32B	0x0
5508	chr9	101495339	101496482	−	ANKS6	0x0
5509	chr9	103086818	103087997	−	TEX10	0x0
5510	chr9	105967533	105968751	+	CYLC2	0x0
5511	chr9	108456322	108457519	+	TMEM38B	0x0
5512	chr9	108535853	108537110	+	TMEM38B	0x0
5513	chr9	108651081	108652249	+	TMEM38B	0x0
5514	chr9	110089577	110090784	+	RAD23B	0x0
5515	chr9	111650030	111651171	−	IKBKAP	0x0
5516	chr9	111778364	111779477	−	C9orf5	0x0
5517	chr9	111780160	111781373	−	C9orf5	0x0
5518	chr9	111790148	111791333	−	C9orf5	0x0
5519	chr9	111812360	111813518	−	C9orf5	0x0
5520	chr9	113016565	113017668	−	TXN	0x0
5521	chr9	113170031	113171232	+	AKAP2	0x0
5522	chr9	113170031	113171232	+	PALM2-AKAP2	0x0
5523	chr9	113740724	113741947	−	LPAR1	0x0
5524	chr9	114176345	114177492	−	KIAA0368	0x0
5525	chr9	114696644	114697810	+	UGCG	0x0
5526	chr9	114796115	114797308	−	SUSD1	0x0
5527	chr9	114802856	114804030	−	SUSD1	0x0
5528	chr9	114980670	114981806	−	PTBP3	0x0
5529	chr9	114993295	114994445	−	PTBP3	0x0
5530	chr9	115013987	115015217	+	HSDL2	0x0
5531	chr9	115248759	115249937	+	KIAA1958	0x0
5532	chr9	115260536	115261678	+	KIAA1958	0x0
5533	chr9	115335902	115337364	+	KIAA1958	0x0
5534	chr9	115346600	115347807	+	KIAA1958	0x0
5535	chr9	115424721	115426125	+	KIAA1958	0x0
5536	chr9	115448029	115450211	−	C9orf80	0x0
5537	chr9	115469920	115471091	−	C9orf80	0x0
5538	chr9	115531377	115532567	+	SNX30	0x0
5539	chr9	115682177	115683415	+	SNX30	0x0
5540	chr9	116023582	116024730	+	SLC31A1	0x0
5541	chr9	116792285	116793484	+	ZNF618	0x0
5542	chr9	116815803	116817028	+	ZNF618	0x0
5543	chr9	116991103	116992232	+	COL27A1	0x0
5544	chr9	117068821	117069994	+	COL27A1	0x0
5545	chr9	117359969	117361206	+	ATP6V1G1	0x0
5546	chr9	117370634	117371856	−	LOC100S0S478	0x0
5547	chr9	120844756	120846132	−	ASTN2	0x0
5548	chr9	123227241	123228507	−	CDK5RAP2	0x0
5549	chr9	123618193	123619372	−	PHF19	0x0
5550	chr9	124101279	124102449	−	STOM	0x0
5551	chr9	124544477	124545706	+	DAB2IP	0x1
5552	chr9	124546847	124548061	+	DAB2IP	0x1
5553	chr9	125641926	125643151	−	RC3H2	0x0
5554	chr9	125641926	125643151	−	SNORD90	0x0
5555	chr9	125842673	125843822	+	RABGAP1	0x0
5556	chr9	126021388	126022620	−	STRBP	0x0
5557	chr9	127115305	127116453	−	PSMB7	0x0
5558	chr9	127194668	127195860	+	GPR144	0x0
5559	chr9	127362373	127363500	+	NR6A1	0x0
5560	chr9	127619641	127620905	−	RPL35	0x0
5561	chr9	128099141	128100376	+	GAPVD1	0x0
5562	chr9	128620793	128622016	+	PBX3	0x0
5563	chr9	128985818	128987014	−	NRON	0x0
5564	chr9	129456477	129457634	+	LMX1B	0x4
5565	chr9	129461350	129462503	+	LMX1B	0x4
5566	chr9	129567385	129568582	+	ZBTB43	0x0
5567	chr9	130209656	130210776	−	RPL12	0x0
5568	chr9	130547783	130548996	+	CDK9	0x0
5569	chr9	130547783	130548996	+	MIR2861	0x0
5570	chr9	130547783	130548996	+	MIR3960	0x0
5571	chr9	130630132	130631339	−	AK1	0x0
5572	chr9	130647627	130648808	−	ST6GALNAC6	0x0
5573	chr9	130886273	130887511	−	PTGES2	0x0
5574	chr9	131101823	131103019	−	TRUB2	0x0
5575	chr9	131369703	131371031	+	SPTAN1	0x2
5576	chr9	131457332	131458528	+	SET	0x2
5577	chr9	131517208	131518346	−	ZER1	0x0
5578	chr9	131668747	131669926	+	LRRC8A	0x0
5579	chr9	131679585	131680770	+	LRRC8A	0x0
5580	chr9	131727918	131729140	+	NUP188	0x0
5581	chr9	131732532	131733679	+	NUP188	0x0
5582	chr9	131770371	131771456	−	SH3GLB2	0x0
5583	chr9	131773181	131774253	−	SH3GLB2	0x0
5584	chr9	131832278	131833404	+	FAM73B	0x0
5585	chr9	132266292	132267491	+	LOC100506190	0x0
5586	chr9	132395806	132396981	+	METTLUA	0x0
5587	chr9	132400461	132402140	−	ASB6	0x0
5588	chr9	132650535	132651858	−	FNBP1	0x2
5589	chr9	132899707	132901024	+	GPR107	0x0
5590	chr9	132995682	132998198	+	NCS1	0x0
5591	chr9	133576846	133578028	+	EXOSC2	0x0
5592	chr9	133580429	133581619	+	EXOSC2	0x0
5593	chr9	133690736	133691950	+	ABL1	0x2
5594	chr9	133924803	133925919	+	LAMC3	0x0
5595	chr9	133996060	133997384	+	AIF1L	0x0
5596	chr9	134287069	134288195	+	PRRC2B	0x0
5597	chr9	134304953	134306142	+	PRRC2B	0x0
5598	chr9	134313808	134315037	+	PRRC2B	0x0
5599	chr9	134319022	134320189	+	PRRC2B	0x0
5600	chr9	134371214	134373009	+	PRRC2B	0x0
5601	chr9	134374644	134375968	+	PRRC2B	0x0
5602	chr9	134451766	134453602	−	RAPGEF1	0x0
5603	chr9	134857136	134858315	−	MED27	0x0
5604	chr9	134913794	134914897	−	MED27	0x0
5605	chr9	135139556	135140719	−	SETX	0x0
5606	chr9	135275910	135277087	−	TTF1	0x0
5607	chr9	135483943	135485086	−	DDX31	0x0
5608	chr9	135784782	135785881	−	TSC1	0x1
5609	chr9	135924729	135925906	−	GTF3C5	0x0
5610	chr9	135973592	135974691	−	RALGDS	0x2
5611	chr9	135998700	136000170	−	RALGDS	0x2
5612	chr9	136020317	136021667	−	RALGDS	0x2
5613	chr9	136203824	136205001	−	SURF6	0x0
5614	chr9	136216397	136217914	+	RPL7A	0x0
5615	chr9	136216397	136217914	+	SNORD36A	0x0
5616	chr9	136216397	136217914	+	SNORD36B	0x0
5617	chr9	136216397	136217914	+	SNORD36C	0x0
5618	chr9	136228108	136230784	−	SURF4	0x0
5619	chr9	136474800	136475979	−	FAM163B	0x0
5620	chr9	137023421	137024790	+	WDR5	0x0
5621	chr9	137029029	137030228	−	RNU6ATAC	0x0
5622	chr9	137305770	137306997	−	RXRA	0x0
5623	chr9	138264957	138266133	+	PPP1R26	0x0
5624	chr9	138651228	138652408	−	CAMSAP1	0x0
5625	chr9	138772916	138775474	−	CAMSAP1	0x0
5626	chr9	138835556	138836655	−	UBAC1	0x0
5627	chr9	139098581	139099758	−	QSOX2	0x0
5628	chr9	139248624	139249755	+	GPSM1	0x0
5629	chr9	139252436	139253615	+	GPSM1	0x0
5630	chr9	139270387	139271514	−	SNAPC4	0x0
5631	chr9	139300843	139302303	−	SDCCAG3	0x0
5632	chr9	139306000	139307223	+	PMPCA	0x0
5633	chr9	139326284	139327462	−	INPP5E	0x0
5634	chr9	139334317	139335518	−	SEC16A	0x0
5635	chr9	139355237	139356585	−	SEC16A	0x0
5636	chr9	139369167	139370266	−	SEC16A	0x0
5637	chr9	139608470	139609690	+	FAM69B	0x0
5638	chr9	139618664	139619796	−	SNHG7	0x0
5639	chr9	139620014	139621238	−	SNHG7	0x0
5640	chr9	139620014	139621238	−	SNORA17	0x0
5641	chr9	139620014	139621238	−	SNORA43	0x0
5642	chr9	139686353	139687562	+	TMEM141	0x0
5643	chr9	139716292	139717458	+	C9orf86	0x0
5644	chr9	139725678	139726811	+	C9orf86	0x0
5645	chr9	139734812	139735981	+	C9orf86	0x0
5646	chr9	139743402	139744501	+	PHPT1	0x4
5647	chr9	139827010	139828223	+	TRAF2	0x0
5648	chr9	139901384	139902524	−	ABCA2	0x0
5649	chr9	139904579	139905686	−	ABCA2	0x0
5650	chr9	139908105	139909204	−	ABCA2	0x0
5651	chr9	139911510	139912639	−	ABCA2	0x0
5652	chr9	139916992	139918141	−	ABCA2	0x0
5653	chr9	139936983	139939048	−	NPDC1	0x0
5654	chr9	139939110	139940262	−	NPDC1	0x0
5655	chr9	139956840	139958016	−	SAPCD2	0x0
5656	chr9	139972957	139974872	+	UAP1L1	0x0
5657	chr9	140001474	140002681	+	MAN1B1	0x0
5658	chr9	140078233	140079809	−	ANAPC2	0x0
5659	chr9	140082995	140084194	+	SSNA1	0x0
5660	chr9	140100452	140101634	+	NDOR1	0x0
5661	chr9	140136707	140137882	+	TUBB4B	0x0
5662	chr9	140147472	140148671	+	C9orf173	0x0
5663	chr9	140169601	140170815	+	C9orf167	0x0
5664	chr9	140279070	140280213	−	EXD3	0x0
5665	chr9	140342309	140343845	−	NELF	0x0
5666	chr9	140351347	140352478	−	NELF	0x0
5667	chr9	140375375	140376591	−	PNPLA7	0x0
5668	chr9	140481200	140482329	−	ZMYND19	0x0
5669	chr9	140484130	140485265	−	ZMYND19	0x0
5670	chr9	140637806	140638965	+	EHMT1	0x0
5671	chr9	140729130	140730908	+	EHMT1	0x0
5672	chr9	141054281	141055394	+	TUBBP5	0x0
5673	chr9	141132390	141133605	+	FAM157B	0x0
5674	chrX	3522243	3523476	−	PRKX	0x2
5675	chrX	6340101	6341264	−	MIR4770	0x0
5676	chrX	8326354	8327513	+	VCX3B	0x2
5677	chrX	9543660	9544882	+	TBL1X	0x0
5678	chrX	9571405	9572643	+	TBL1X	0x0
5679	chrX	9862050	9863191	+	SHROOM2	0x0
5680	chrX	11010346	11011488	−	ARHGAP6	0x0
5681	chrX	14629215	14630428	−	FANCB	0x0
5682	chrX	14876727	14877909	−	FANCB	0x0
5683	chrX	15421374	15422561	−	PIR-FIGF	0x0
5684	chrX	17091194	17092417	+	REP52	0x0
5685	chrX	17300438	17301635	+	NHS	0x0
5686	chrX	18372174	18373364	−	SCML2	0x0
5687	chrX	20153607	20154922	−	EIF1AX	0x0
5688	chrX	20153607	20154922	−	SCARNA9L	0x0
5689	chrX	21576566	21577762	+	CNKSR2	0x0
5690	chrX	22229861	22231058	+	PHEX	0x0
5691	chrX	24095005	24096156	+	EIF2S3	0x0
5692	chrX	24175280	24176442	+	ZFX	0x0
5693	chrX	24196894	24198305	+	ZFX	0x0
5694	chrX	24761177	24763241	+	POLA1	0x0
5695	chrX	24761177	24763241	+	SCARNA23	0x0
5696	chrX	24977492	24978688	+	POLA1	0x0
5697	chrX	27399828	27401046	−	SMEK3P	0x0
5698	chrX	29000399	29001566	−	DCAF8L1	0x0
5699	chrX	30648152	30649398	+	GK	0x0
5700	chrX	34233500	34234721	+	FAM47B	0x0
5701	chrX	39645752	39646886	−	BCOR	0x2
5702	chrX	40464569	40465726	+	ATP6AP2	0x0
5703	chrX	41092038	41093252	+	USP9X	0x0
5704	chrX	41207726	41208825	+	DDX3X	0x1
5705	chrX	44736213	44737379	+	KDM6A	0x2
5706	chrX	46299524	46300707	−	ZNF674	0x0
5707	chrX	47081266	47082479	+	CDK16	0x0
5708	chrX	47088062	47089227	+	CDK16	0x0
5709	chrX	47495209	47496359	−	ELK1	0x0
5710	chrX	47665780	47667007	+	ZNF81	0x0
5711	chrX	47746834	47748055	+	ZNF81	0x0
5712	chrX	48435453	48436647	+	RBM3	0x0
5713	chrX	48462703	48463818	+	WDR13	0x0
5714	chrX	48831187	48832583	−	GRIPAP1	0x0
5715	chrX	49126721	49127934	−	PPP1R3F	0x0
5716	chrX	49857672	49858823	+	CLCN5	0x2
5717	chrX	51936036	51937238	+	MAGED4	0x0
5718	chrX	51936036	51937238	+	MAGED4B	0x0
5719	chrX	53106605	53107796	+	GPR173	0x0
5720	chrX	53134334	53135497	+	TSPYL2	0x0
5721	chrX	53405372	53407332	−	SMC1A	0x0
5722	chrX	53569946	53571046	−	HUWE1	0x0
5723	chrX	53618943	53620070	−	HUWE1	0x0
5724	chrX	53673766	53675041	−	HUWE1	0x0
5725	chrX	53792619	53793775	−	HUWE1	0x0
5726	chrX	54594744	54595938	+	GNL3L	0x0
5727	chrX	54596140	54597311	+	GNL3L	0x0
5728	chrX	56992161	56993336	−	SPIN3	0x0
5729	chrX	68004807	68006025	+	EFNB1	0x0
5730	chrX	68379551	68380728	−	PJA1	0x0
5731	chrX	68891771	68893024	+	EDA	0x0
5732	chrX	69380277	69381519	+	IGBP1	0x0
5733	chrX	69531191	69532421	+	KIF4A	0x0
5734	chrX	69691179	69692344	+	DLG3	0x2
5735	chrX	69720649	69721848	+	DLG3	0x2
5736	chrX	70182424	70183623	+	FOXO4	0x1
5737	chrX	70507281	70508462	−	ZMYM3	0x0
5738	chrX	70520333	70521503	+	NONO	0x2
5739	chrX	70602894	70604095	+	TAF1	0x2
5740	chrX	70861969	70863207	+	ACRC	0x0
5741	chrX	71570013	71571157	−	HDAC8	0x0
5742	chrX	71596356	71597548	−	HDAC8	0x0
5743	chrX	71769793	71770972	−	HDAC8	0x0
5744	chrX	73046559	73048327	−	XIST	0x4
5745	chrX	73052516	73053845	−	XIST	0x4
5746	chrX	73057033	73059270	−	XIST	0x4
5747	chrX	73062806	73063994	−	XIST	0x4
5748	chrX	73069685	73073030	−	XIST	0x4
5749	chrX	73170342	73171562	+	JPX	0x0
5750	chrX	73430482	73431552	−	MIR421	0x0
5751	chrX	73436680	73437810	−	MIR421	0x0
5752	chrX	73482382	73483604	−	FTX	0x0
5753	chrX	73494914	73496013	−	FTX	0x0
5754	chrX	76923431	76924656	−	ATRX	0x2
5755	chrX	77081697	77082848	−	MAGT1	0x0
5756	chrX	77105733	77106914	−	MAGT1	0x0
5757	chrX	79927079	79928302	−	BRWD3	0x0
5758	chrX	81950478	81951677	−	RPS6KA6	0x1
5759	chrX	85340420	85341609	−	CHM	0x0
5760	chrX	96438715	96439906	+	DIAPH2	0x0
5761	chrX	99410666	99411825	−	PCDH19	0x0
5762	chrX	100289732	100290890	−	TRMT2B	0x0
5763	chrX	100654698	100655907	−	GLA	0x0
5764	chrX	100668386	100669571	+	HNRNPH2	0x0
5765	chrX	100668386	100669571	+	RPL36A-HNRNPH2	0x0
5766	chrX	100678736	100679933	+	ARMCX4	0x0
5767	chrX	102108868	102110010	+	LOC100287765	0x0
5768	chrX	102185541	102186736	+	RAB40AL	0x0
5769	chrX	102632229	102633433	+	NGFRAP1	0x0
5770	chrX	102930316	102931634	−	MORF4L2	0x0
5771	chrX	103407200	103408423	+	FAM199X	0x0
5772	chrX	103416323	103417521	+	FAM199X	0x0
5773	chrX	105855261	105856451	+	CXorf57	0x0
5774	chrX	106164212	106165373	−	R1PPLY1	0x0
5775	chrX	106184082	106185253	−	MORC4	0x0
5776	chrX	106236843	106238032	−	MORC4	0x0
5777	chrX	106296930	106298133	−	RBM41	0x0
5778	chrX	106312517	106313695	−	RBM41	0x0
5779	chrX	106351735	106352899	−	RBM41	0x0
5780	chrX	106956061	106957210	−	TSC22D3	0x0
5781	chrX	107083544	107084738	+	MID2	0x0
5782	chrX	107330418	107331641	−	PSMD10	0x0
5783	chrX	107692109	107693273	+	COL4A5	0x0
5784	chrX	107755369	107756586	+	COL4A5	0x0
5785	chrX	107962711	107965128	−	IRS4	0x2
5786	chrX	107965833	107966886	+	IRS4	0x2
5787	chrX	107978161	107979977	−	IRS4	0x2
5788	chrX	108296815	108298321	+	COL4A5	0x0
5789	chrX	108885425	108886557	−	ACSL4	0x0
5790	chrX	109418043	109419259	+	TMEM164	0x0
5791	chrX	109419535	109421324	+	TMEM164	0x0
5792	chrX	109440950	109442127	−	AMMECR1	0x0
5793	chrX	110928049	110929158	+	ALG13	0x0
5794	chrX	111556247	111557485	−	ZCCHC16	0x0
5795	chrX	112018825	112019925	−	AMOT	0x0
5796	chrX	112832649	112833826	−	AMOT	0x0
5797	chrX	114388539	114389720	−	LRCH2	0x0
5798	chrX	114860238	114861417	−	LRCH2	0x0
5799	chrX	114883597	114884758	+	PLS3	0x0
5800	chrX	114937422	114938740	+	PLS3	0x0
5801	chrX	114952760	114953901	−	LRCH2	0x0
5802	chrX	115033924	115035353	−	CXorf61	0x0
5803	chrX	115051152	115052326	−	cxorf61	0x0
5804	chrX	115108241	115109440	−	CXorf61	0x0
5805	chrX	117333430	117334585	−	KLHL13	0x0
5806	chrX	117512110	117513293	+	WDR44	0x0
5807	chrX	118151592	118152740	+	LONRF3	0x0
5808	chrX	118377285	118378507	+	PGRMC1	0x0
5809	chrX	118557172	118558436	+	SLC25A43	0x0
5810	chrX	118603146	118604243	+	SLC25A5	0x0
5811	chrX	118717249	118718392	+	UBE2A	0x2
5812	chrX	118919904	118921072	−	RPL39	0x0
5813	chrX	119005351	119006450	+	NDUFA1	0x0
5814	chrX	119390792	119391981	+	ZBTB33	0x0
5815	chrX	119658057	119660511	−	CUL4B	0x0
5816	chrX	122736393	122737568	−	THOC2	0x0
5817	chrX	123041693	123042887	+	XIAP	0x0
5818	chrX	123095598	123096767	+	STAG2	0x0
5819	chrX	123234731	123236864	+	STAG2	0x0
5820	chrX	128705605	128706804	+	OCRL	0x0
5821	chrX	128725857	128727037	+	OCRL	0x0
5822	chrX	129065075	129066245	−	ZDHHC9	0x0
5823	chrX	129535551	129536727	−	GPR119	0x0
5824	chrX	129538199	129539389	+	RBMX2	0x0
5825	chrX	130882834	130884008	−	LOC286467	0x0
5826	chrX	130889093	130890323	−	LOC286467	0x0
5827	chrX	130902059	130903202	−	LOC286467	0x0
5828	chrX	130917396	130918579	−	LOC286467	0x0
5829	chrX	130927787	130929004	−	LOC286467	0x0
5830	chrX	131198110	131199259	+	MST4	0x0
5831	chrX	131337023	131338180	−	RAP2C	0x0
5832	chrX	131512145	131513234	−	MBNL3	0x0
5833	chrX	131760858	131762133	−	HS6ST2	0x0
5834	chrX	132081206	132082401	−	HS6ST2	0x0
5835	chrX	132435951	132437179	−	GPC4	0x0
5836	chrX	132804697	132805894	+	CCDC160	0x0
5837	chrX	133682855	133684020	−	MIR424	0x0
5838	chrX	133683746	133684962	+	LOC100506757	0x0
5839	chrX	133693934	133695138	+	LOC100506757	0x0
5840	chrX	133750415	133751607	−	PLAC1	0x0
5841	chrX	133904208	133905344	−	FAM122B	0x0
5842	chrX	134169327	134170543	+	FAM127A	0x0
5843	chrX	134685389	134686586	+	DDX26B	0x0
5844	chrX	134700591	134701697	+	DDX26B	0x0
5845	chrX	134704442	134705586	+	DDX26B	0x0
5846	chrX	135044994	135047017	−	MMGT1	0x0
5847	chrX	135292161	135293316	+	FHL1	0x0
5848	chrX	135894541	135895736	−	ARHGEF6	0x0
5849	chrX	135960801	135962006	−	RBMX	0x1
5850	chrX	135960801	135962006	−	SNORD61	0x0
5851	chrX	138051867	138053046	+	LOC100129662	0x0
5852	chrX	138822633	138823803	−	ATP11C	0x0
5853	chrX	139806745	139807946	+	RP1-177G62	0x0
5854	chrX	144138226	144139456	+	SPANXN1	0x0
5855	chrX	147024021	147025185	+	FMR1	0x0
5856	chrX	147743371	147744594	+	AFF2	0x2
5857	chrX	148615669	148616861	−	LOC100131434	0x0
5858	chrX	148622764	148623954	+	CXorf40A	0x0
5859	chrX	149101387	149102530	−	CXorf40B	0x0
5860	chrX	149283200	149284299	+	LOC100272228	0x0
5861	chrX	149932765	149933963	+	MTMR1	0x0
5862	chrX	149934398	149936217	−	CD99L2	0x0
5863	chrX	150156335	150157614	+	HMGB3	0x0
5864	chrX	150347357	150348535	+	GPR50	0x0
5865	chrX	152138729	152139828	+	ZNF185	0x0
5866	chrX	152615120	152616281	+	ZNF275	0x0
5867	chrX	152712573	152713786	−	HAUS7	0x0
5868	chrX	152907741	152908844	+	DUSP9	0x2
5869	chrX	152931282	152932454	+	DUSP9	0x2
5870	chrX	152961002	152962294	+	SLC6A8	0x0
5871	chrX	153061339	153062580	+	SSR4	0x0
5872	chrX	153212601	153214292	−	HCFC1	0x0
5873	chrX	153229508	153230711	−	HCFC1	0x0
5874	chrX	153275908	153277630	−	IRAK1	0x0
5875	chrX	153282970	153284121	−	IRAK1	0x0
5876	chrX	153290837	153291997	−	MECP2	0x0
5877	chrX	153329200	153330332	−	MECP2	0x0
5878	chrX	153582804	153583968	−	FLNA	0x2
5879	chrX	153590352	153591533	−	FLNA	0x2
5880	chrX	153607528	153608725	+	EMD	0x0
5881	chrX	153626228	153627408	+	RPL10	0x1
5882	chrX	153648801	153649993	+	TAZ	0x0
5883	chrX	153656522	153657630	+	ATP6AP1	0x0
5884	chrX	153663803	153666133	+	ATP6AP1	0x0
5885	chrX	153663803	153666133	+	GDI1	0x0
5886	chrX	153670936	153672130	+	GDI1	0x0
5887	chrX	153677138	153678294	+	FAM50A	0x0
5888	chrX	153736962	153738109	−	FAM3A	0x0
5889	chrX	153743942	153745077	−	FAM3A	0x0
5890	chrX	153996235	153997439	+	DKC1	0x0
5891	chrX	153996235	153997439	+	SNORA36A	0x0
5892	chrX	154002693	154003854	+	DKC1	0x0
5893	chrX	154002693	154003854	+	SNORA56	0x0

Lengthy table referenced here
US20220403380A1-20221222-T00001
Please refer to the end of the specification for access instructions.

OTHER EMBODIMENTS

It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

LENGTHY TABLES
The patent application contains a lengthy table section. A copy of the table is available in electronic form from the USPTO web site (https://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20220403380A1). An electronic copy of the table will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).

SEQ ID NO.

Chromosome

Start (bp)

Nearest gene

1.-36. (canceled)

37. A method of reducing expression of a target interleukin 1 receptor-associated kinase 1 (IRAK1) gene in a cell, the method comprising delivering to the cell a single stranded oligonucleotide of 15 to 40 nucleotides in length having a region of complementarity that is complementary with at least 15 contiguous nucleotides of an IRAK1 RNA, wherein the oligonucleotide binds to or within 500 nt of SEQ ID NOs: 5874, 5875, 17389, 17390, or 17391, wherein PRC1 binding to the IRAK1 RNA is disrupted.

38.-41. (canceled)

42. The method of claim 37, wherein the cell is in vitro.

43. The method of claim 37, wherein the cell is in vivo.

44. The method of claim 37, wherein at least one nucleotide of the oligonucleotide is a modified nucleotide.

45.-48. (canceled)

49. The method of claim 37, wherein the oligonucleotide has complementarity to the IRAK1 RNA in a region of the IRAK1 RNA that forms a stem-loop structure.

50. (canceled)

51. The method of claim 37, wherein at least one nucleotide of the oligonucleotide is a ribonucleic acid analogue comprising a ribose ring having a bridge between its 2′-oxygen and 4′-carbon.

52. The method of claim 51, wherein the ribonucleic acid analogue comprises a methylene bridge between the 2′-oxygen and the 4′-carbon.

53. The method of claim 37, wherein at least one nucleotide of the oligonucleotide comprises a modified sugar moiety.

54. The method of claim 53, wherein the modified sugar moiety comprises a 2′-O-methoxyethyl modified sugar moiety, a 2′-methoxy modified sugar moiety, a 2′-O-alkyl modified sugar moiety, or a bicyclic sugar moiety.

55. The method of claim 37, wherein the oligonucleotide comprises at least one modified internucleoside linkage.

56. The method of claim 55, wherein the at least one modified internucleoside linkage is selected from phosphorothioate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethyl ester, and combinations thereof.

57. The method of claim 37, wherein the oligonucleotide is configured such that hybridization of the single stranded oligonucleotide to the PRC1-binding RNA does not activate an RNAse H pathway in the cell.

58.-61. (canceled)

62. The method of claim 37, wherein the cell is a cell of a male subject.

63.-67. (canceled)

68. A method of isolating RNA sequences that interact with a selected protein, e.g., with chromatin complexes, in a cell, the method comprising:

providing a cell expressing (i) a biotin ligase, e.g., BirA, and (ii) the protein of interest comprising a biotinylation sequence;

exposing the cells to UV-crosslinking;

lysing the cells,

isolating protein-RNA complexes from the lysed cells, e.g., using avidin purification, e.g., streptavidin beads;

washing the complexes in protein-denaturing conditions, e.g., high salt and detergent, e.g., using 8 M urea+0.1% SDS; and

isolating the protein-RNA complexes.

69.-75. (canceled)

76. A method for treating a subject with systemic lupus erythematosis, the method comprising administering a therapeutically effective amount of an inhibitory nucleic acid targeting a PRC1-binding region on IRAK1 RNA, preferably wherein the PRC1 binding region comprises SEQ ID NO:5874, 5875, or 17389-17391.

77. The method of claim 76, comprising administering an inhibitory nucleic acid targeting a sequence within the 3′UTR of IRAK1.

78. (canceled)

79. The method of claim 76, wherein the inhibitory nucleic acid comprises at least one locked nucleotide (LNA).

80.-83. (canceled)

84. The method of claim 37, wherein the oligonucleotide binds to or within 100 nt of SEQ ID NOs:5874, 5875, 17389, 17390, or 17391.

85. The method of claim 37, wherein the oligonucleotide binds to or within SEQ ID NOs: 5874, 5875, 17389, 17390, or 17391.