CN100427603C - 调控外源基因转录的方法 - Google Patents

调控外源基因转录的方法 Download PDF

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CN100427603C
CN100427603C CNB008138680A CN00813868A CN100427603C CN 100427603 C CN100427603 C CN 100427603C CN B008138680 A CNB008138680 A CN B008138680A CN 00813868 A CN00813868 A CN 00813868A CN 100427603 C CN100427603 C CN 100427603C
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L-P·维吉纳
M-A·德奥斯特
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Abstract

本发明涉及一种在遗传修饰的生物中调节转基因转录的方法。更具体地，本发明涉及带有目的基因编码序列的表达载体的用途，其中所述目的基因在启动序列的转录控制之下，该启动序列的活性由氮的存在来调控。

Description

调控外源基因转录的方法
发明背景
(a)发明领域
本发明涉及在遗传改变的生物中调控转移基因转录的方法。更特异地，本发明涉及含有在启动子序列(其活性受氮存在调控)转录控制下的目的基因编码序列之表达载体的用途。优选地，该构建体用于转基因豆科植物(例如大豆、苜蓿、牛角花三叶草、鸟足三叶草、豆、豌豆、花生)，其生长不受无机氮缺乏影响，而且在发育的任何给定时期通过加入合适的氮源都能进行诱导表达。本发明在更广泛的范围内能用于通过加入任何氮源之任何给定转移基因的诱导表达，只要该生物在缺乏该氮诱导物时能够充分生长；例如在植物界，浮萍(Lemnaminor)能在硝酸盐或铵为氮源时适应性生长；因此转基因浮萍能在硝酸盐为唯一氮源时生长，并且通过添加铵来引发转移基因的表达，只要表达盒含有靠加入铵来启动表达的来自天然基因的启动子。因此本发明提供了在任一生物中通过加入多种氮诱导物来调控转移基因特性之表达的方法。
(b)现有技术描述
氮是生命中必需的分子。所有活生物需要氮以合成氨基酸(蛋白质的构建单元)和核苷酸(核酸的构建单元)。硝酸铵是优选的以化肥形式提供给农作物的的无机氮形式。通过大多数草本植物共同的代谢途径的活性，硝态氮先还原为亚硝酸盐再还原为铵。依赖其种属，部分或所有吸收的硝酸盐在其还原为铵以前，通过木质部移到叶细胞。铵、或其它还原形式的氮也通过根系统被吸收(尽管通常效率较低)，但是它们的同化作用不需要还原。这些新吸收的铵或含有铵的分子加入细胞中内源性库，其通过氨基酸和其它氮源分子由铵循环形成。某些种属不易代谢硝态氮，因而不能依赖硝酸盐作为唯一氮源；许多针叶属归为后一类。荚果和其它共生植物种属形成植物王国里第三大类氮使用者。它们通过微生物固定气态氮并与之形成代谢联盟。植物有效利用还原氮生长，因此，这些农作物通过得到土壤中的无机氮能够独立发育。
许多微生物和野生植物种属充分适应了氮源的可得性，因而能在缺乏分子形式氮时完成其生命周期，如果在另一生长环境里能得到，它们能够专一并有效地利用氮源。像大多数同化途径一样，氮同化在细胞中受严谨调控。例如，在各种微生物和植物种属中广泛描述了(综述见Miflin和Lea，第5和12册，植物生物化学(The Biochemistry ofPlant)编码硝酸还原酶(NaR)和亚硝酸还原酶(NiR)(负责还原硝酸盐为铵)的基因的表达。尽管硝酸盐不是参与控制NaR和NiR表达的唯一调控分子，它的存在对起始最终导致这些基因持续转录和翻译的转导级联事件很重要。可见，豆科植物当在缺乏无机氮生长时NaR和NiR基因的表达被抑制。
在某些植物种属中鉴定了NiR启动子(Back等，1991，植物分子生物学(Plant Molecular Biology)17：9-18；Sander等，1995，植物分子生物学27：165-177)。在转基因植物中用报告基因表征了这些启动子的可诱导性，表明需要获得硝酸盐以完全活化转录。
还描述了其它氮源的同化途径，并表征了参与某些路径的基因的启动子。
近15年来遗传转化的微生物被用于生产有用的重组分子，目前正应用于制药、化妆品和护肤品工业。在过去10年里随着将这一普通概念应用到复杂真核生物所需技术的发展，该技术已经从微生物扩展到植物和动物。基本上，编码目的蛋白的基因或者编码负责代谢途径改变产生某种目的分子的酶的基因，以适当的方式与顺式和反式作用调控序列相连，并传递给靶细胞，其以瞬时的或稳定的方式整合到分子机器中。转基因细胞或从转基因细胞再生的组织或生物接着进行转移基因的转录和翻译，从而能够积累目的蛋白，或通过目的酶的活性进行新的代谢反应。
正在出现的分子农业工业(在动物或农作物中生产重组分子)是即将到来的下一世纪最有前景的产业之一。其前景是为工业提供安全和再生分子工厂。目前发展的应用有：生产供治疗和诊断用的低成本单克隆抗体；生产用于治疗慢性或致死性疾病的大量的激素、细胞因子和其它生物活性分子；生产多种血液成分的生物安全替代品；生产用于食品和造纸工业的大量加工酶；生产用于废物处理的低成本酶；以及生产用于化妆品工业的安全的生物活性分子。
这项技术应用的局限常常是由于转基因生物不能积累足够量的重组产品，其原因是由于低的转录效率、信使不恰当的剪接、外源mRNA的不稳定、低的翻译效率、重组蛋白对内源性蛋白酶的超敏感性、或者是重组生物对外源蛋白的超敏感性导致不恰当的和有限的生长，或最坏时对宿主生物产生强的有害效应。当边际利润低、或当处理或处置残余物质导致生物安全或环境问题时，生产水平的不足直接影响应用发展。所需重组产品积累水平的提高是保证分子农业许多应用商业化的一个关键因素。
建议使用可诱导性启动子，并且在某些情况下成功地使用，以抵消所有上述因子联合效果。强的可诱导性启动子成功地产生高的暂时转录效率，其导致外源mRNA和翻译产物的高的暂时积累。因此，当表达的可诱导性与足够的同步蛋白质复性步骤相匹配，获得的每单位的产量比使用组成型表达要高。
研发了几个含可诱导性启动子的表达盒用于微生物生产系统，其中一些目前可用于研究目的。一些可诱导性启动子目前正用于植物(创伤诱导性)或动物(对哺乳动物腺细胞(PPL)特异的)系统，尽管没有利用低成本且生物安全的化学诱导物(如硝酸盐)的报告。
提供调控转移基因在遗传改造的生物中转录的方法是非常可取的。
发明概述
本发明的一个目的是提供调控转移基因在遗传改造生物中转录的方法。
本发明的另一个目的是提供含在启动序列(其活性受氮存在调控)转录控制下之目的基因编码序列的表达载体的用途。
本发明涉及氮可诱导性表达盒用于将外源基因在植物中可控制表达的用途。从以下描述可见，可分离该调控序列，使顺式作用序列适当地与目的基因开放阅读框架相连，由此其转录受加入的特异性氮源控制。
本发明的一个方面，靶系统使用豆科植物种类，因此，如果转基因植物在无硝酸盐培养基上生长，含有氮可诱导性启动子的构建体将在生长期持续低水平转录，从而使得植物生物量积累不会受转基因特征的干扰。加入硝酸盐到生长培养基后，随后几天内相对大量的生物量会被诱导转录。优化诱导时间，进行蛋白质积累以最大量得到的所需重组产品。
尽管以下描述阐明：本发明方便地适合对硝酸盐缺乏的转基因豆科植物之硝酸盐诱导，应该记住，该通用概念也能用于研发其它生产系统，从微生物、植物和动物领域里的多种氮同化系统获益。
在本发明的另一方面，在不通过共生联系进行氮固定的、但可利用多种氮资源(还原的或氧化的)生长的，并因此具有当生长环境里缺乏氮源底物使其氮同化途径之一失活也能充分生长的能力之生物中，氮可诱导性也用于蛋白质最大量生产。利用控制该失活途径中任何基因的转录以驱动目的基因在该生物中表达的表达盒，使得一旦加入以前缺乏的氮源性复合物时，转基因性状可诱导性表达。例如，浮萍是能在硝酸盐或铵中生长的植物；本发明能用于开发带有与目的基因适宜连接的铵可诱导性启动子之表达盒，以使硝酸盐中生长型转基因浮萍植物可被诱导。
按照本发明，提供了调控外源基因在转基因生物中转录的方法，包括如下步骤：
a)用表达构建体制备转基因生物，其中所述构建体至少包含氮可诱导性启动子以及基因的开放阅读框架，其中启动子具有选自SEQ IDNOS：1-13的序列和功能性片段及其衍生物，其中所述启动子与所述外源基因可操作地定位以表达所述基因。
按照本发明优选的实施方案，该方法可进一步包括通过加入或去除氮诱导物调控所述基因转录表达的步骤。
按照本发明优选的实施方案，提供了一种调控外源基因在转基因生物中转录的方法，包括：
a)制备表达构建体，其至少包括一个有或无顺式作用序列的氮可诱导性启动子、基因的开放阅读框架以及在所述构建体3’末端的多聚腺苷酸化信号终止位点，其中所述启动子与所述基因可操作地定位以表达所述基因为了所述基因的转录表达，通过加入或去除氮诱导物来调控该启动子；
b)亚克隆步骤a)的构建体到所述生物的合适转染载体；
c)转移所述载体到所述生物或其细胞的DNA中；并且
d)在合适的培养基上选择转基因体。
按照本发明优选的实施方案，该方法进一步包括以下步骤：
e)将载体导入到合适的根癌土壤杆(Agrobacterium tumefaciens)菌株；
f)使用步骤a)的土壤杆菌株转移T-DNA到植物细胞；
g)在合适培养基中选择所述植物细胞的转基因体；
h)从所述转移基因细胞再生胚或小植株；并且
i)从所述再生胚长为成熟植物。
按照本发明优选的实施方案，可从苜蓿中表达的Nir基因5’上游区域分离顺式作用序列。
按照本发明方法优选的实施方案，所述启动子具有SEQ IDNO：1-13所示的序列和功能性片段及其衍生物。
按照本发明优选的实施方案，生物是植物，更优选地双子叶植物。
按照本发明优选的实施方案，生物是苜蓿或烟草。
按照本发明优选的实施方案，氮诱导物是硝酸盐。
按照本发明优选的实施方案，DNA转移方法是任何合适的转移方法，包括DNA轰击、电穿孔、PEG介导的DNA转移和颈须噬菌体，等等。
按照本发明优选的实施方案，表达构建体包含至少一种氮可诱导性启动子和至少一种顺式或反式作用元件。
按照本发明优选的实施方案，生物是植物、真菌、细菌、酵母或动物。
按照本发明优选的实施方案，从任一参与氮同化途径的基因5’上游区域分离启动子或顺式作用序列。
按照本发明优选的实施方案，从任何其转录受给定氮源的获得调控的基因5’上游区域分离启动子或顺式作用序列。
按照本发明优选的实施方案，启动子或顺式作用序列是其转录活性受在任何活生物环境中任何氮源的加入或去除调控的任何序列。
按照本发明优选的实施方案，从其中分离了启动子或顺式作用序列的生物是任何植物、真菌、酵母、细菌或动物。
按照本发明优选的实施方案，提供了用于增强外源基因在转基因生物中转录的启动子，其包含有/无顺式作用序列的氮可诱导性启动子以表达所述基因，并且被改造成通过加入或去除氮诱导物来调控，用于所述基因的转录表达。
优选地，启动子具有选自SEQ ID NOS：1-13所示的序列和功能性片段及其衍生物。
按照本发明优选的实施方案，提供了与启动子联合使用使得外源基因在转基因生物中表达的终止子，其包含为在所述基因3’末端插入的多聚腺苷酸化信号终止位点，其中所述终止子与所述基因和所述启动子可操作地定位，由此允许所述基因表达。
优选地，终止子具有选自SEQ ID NOS：14-16所示的序列和功能性片段及其衍生物。
用于本发明的下列术语定义如下：
“功能性片段或其衍生物”的表述是指序列SEQ.ID.NOS：1-16的任何衍生物或片段，其可使外源基因得到与SEQ.ID.NOS：1-13所示本发明的启动子或SEQ.ID.NOS：14-16所示本发明的终止子相当的表达水平。
附图说明
图1表示，在硝酸盐营养植物之前(空心柱)和之后(实心柱)，在转基因烟草植物叶中使用启动子Nir(SEQ ID NOS：2-13)和终止子NOS之GUS表达水平。按照方法部分中的描述，用功能性定位的全长的和缺失的苜蓿NiR启动子和NOS终止子转化烟草植物，来控制GUS报告基因的转录和终止。在硝酸盐诱导前后按照Jefferson等(1987，EMBO J.13：3901-3907)测定GUS活性。
图2表示，在硝酸盐营养植物之前(空心柱)和之后(实心柱)，在转基因烟草植物叶中使用启动子Nir(SEQ ID NOS：2，3，5-6)和终止子Nir(SEQ ID NOS：15-16)之GUS表达水平。按照下面的材料与方法中的描述，用功能性定位的全长的和缺失的苜蓿NiR启动子和NOS终止子转化烟草植物，来控制GUS报告基因转录和终止。在硝酸盐诱导前后按照Jefferson(1987，EMBO J.13：3901-3907)测定GUS活性。
图3表示，在硝酸盐营养植物之前(空心柱)和之后(实心柱)，在结瘤的转基因苜蓿植物叶中使用启动子NiR和终止子NoS之GUS表达水平如图3所示。按照Khoudi等(1997，Gene197：343-351)描述，用功能性定位的构建体GC2-E，GC2-B，DC1-D和35S转化基因型为11.9的苜蓿以驱动报告基因GUS的表达。再生后，转基因植物转移到无菌的蛭石上，并用根瘤菌属(Rhizobium)株的Balzac(Nitragin)接种。反复加入无硝酸盐的Hoagland’s溶液让植物生长3周；然后按照Jefferson等(1987，EMBO J 13：3901-3907)描述，测定第一片完全扩展叶中GUS的活性。植物再用40mM硝酸盐施肥2天。再次测定第一片完全扩展叶中GUS活性。此处显示数据为硝酸盐诱导前后GUS比活性的比率。
发明详述
以下详细描述了用来产生能够调控其中报告基因表达的转基因烟草和苜蓿系的方法。可对可以分离氮可诱导性启动子的方法；可以将其连接到用于在植物中表达的构建体的开放阅读框架的方法；可以使用并空间排列构建体的不同顺式和反式作用元件的方法；证明并利用氮的可诱导性的方法加以变化，应该记住以上诸多变化均落在本发明范围内。
在该实施方案中，从苜蓿中用RT-PCR方法，用由植物NiR共有序列推断的引物，首次分离了NiR的cDNA链。再用cDNA链去进行上游/下游基因组步移。然后功能性定位NiR启动子区域和缺失、5’UTR和NiR终止子，以控制报告基因GUS的转录和终止。按照Desgagnes等(1995，植物细胞组织器官培养(Plant Cell Tissue OrganCult.)42：129-140)描述，将该构建体插到合适的表达载体，所述载体用于DNA轰击至烟草和苜蓿叶中，以及用于土壤杆菌介导的DNA转移。这两种DNA转移方法用于证明，通过向培养基中加入或去除硝酸盐可以调控报告基因的表达。
材料与方法
生物材料
大肠杆菌DH5α用于进行所有克隆步骤，基因型11.9耐寒苜蓿用于所有实验，包括使用根癌土壤杆菌感染稳定转化。(Desgagnes et al.1995，植物细胞组织器官培养42：129-140)
分离总RNA
主要按照de Vries等(1988，B6第1页，Gevin SB Shilperoot RA编，植物分子生物学手册(Plant Molecular Biology Manual)，Dordrecht：Kluwer Academic Publisher)描述的热酚法抽提总RNA。
RT-PCR
用RT-PCR生产来自叶细胞总mRNA的对应于一种丰富的NiRmRNA的DNA片段。从五个公共植物NiR开放阅读框架，即Genbank序列#AB006032(Arabidopsis Nir mRNA)、#X66145(烟草部分NiRmRNA)、#U10419(大豆全NiR编码区)、#X07568(菠菜NiRmRNA)、和#U90429(甘氨酸max NiR全编码区)，第一次鉴定保守区。从两个保守区，即编码链5’末端的Nir5-5’GATATTGATGTTAGACTCAAGTGGC3’(SEQ ID NO：17)，和3’末端的Nir3-5’CACYSATTCCACTTCCTWGGC3’，推导出简并寡核苷酸。首先用200单位M-MLV逆转录酶(RT)、1μg叶细胞总RNA、4mM dNTP(每种各1mM)、5μM随机六聚体引物在1X M-MLV-RT缓冲液(50mM Tris-HCl，pH 8.3，75mM KCl，3mM MgCl2)中在37℃条件下反应1小时，进行逆转录反应。PCR反应在Perkin ElmerCetus GenAmp PCR 9600系统(EG&G，Wellesley，MA)中进行，在1X PCR缓冲液(20mM Tris-HCl pH 8.4，50mM KCl，2mM MgCl2)中使用2.5单位Taq DNA聚合酶、2μM Nir5引物、2μM Nir3引物、800μM dNTP(每种各200μM)。使用的循环程序是：起始94℃4分钟，然后94℃1分钟，55℃30秒，72℃3分钟做30个循环。该程序还包括72℃延伸7分钟。
DNA测序
DNA测序按照Sanger等(1997，P.N.A.S.USA，74：5643-5647)描述的进行。
基因组步移
用Clontech实验室通用基因组步移试剂盒(Palo Alto.CA)(Cat.#1807-1)进行从RT-PCR反应克隆的苜蓿Nir cDNA片段的上游步移。用于扩增编码序列上游序列的NiR特异性常规引物是：
Nir1106r-5’TTGTCACATCAGCACATCCGTCTTTGC 3’(SEQID NO：19)，和
Nir1061r-5’TCGCCAAGTATCTTGTTTGAGCACTTG 3’(SEQID NO：20)。
扩增的3775bp片段亚克隆到pGEM-TEasy载体(Promega，Madison，WI)(Cat.#A1360)中进一步分析。所得质粒命名为pGNir4c。
用下述NiR特异性引物按上游步移进行下游步移：
Nir1c-5’ATGTCTTCCTTCTCAGTACGTTTCCTC 3’(SEQ IDNO：28)，和
Nir138c-5’CAAGTTGATGCATCAAGGTGGGAGCCTAGA 3’(SEQ ID NO：29)。
扩增的3508bp片段亚克隆到pGEM-Teasy载体(Promega，Madison，WI)(Cat.#A1360)中进一步分析，所得质粒命名为PGN3’1。
构建表达盒与载体
使用GUS报告基因的表达分析盒构建如下。用HindIII和EcoRI从pBI101消化无启动子的GUS盒，插到pUC19多克隆位点的HindIII与EcoRI位点中。所得质粒命名为pBI201并用于进一步构建。用通用基因组步移试剂盒中AP2引物作为上游定位引物，PCR扩增Nir上游序列，并且任一常规设计下游引物以SmaI限制位点结束。该四种引物分别定位于基因的5’非翻译区(Nir-23r-Sma-5’AGAGCCGGGAGAAGAGAGTGTGTTTG 3’)(SEQ ID NO：21))、转运肽编码序列末端(Nir51r-Sma-5’TTCTCCCGGGGGACGAGAGATGGATGGT3’)(SEQ ID NO：22))、转运肽编码序列后50bp(Nir103r-Sma-5’TTCTCCCGGGGTTGAA-ACAGGTGCAACTGA3’)(SEQ ID NO：23))和转运肽编码序列后100bp(Nir158r-Sma-5’TTCTCCCGGGTAACCATCTTTTTCCTCA 3’)(SEQ ID NO：24))。以pGNir4c质粒为模板按标准条件进行扩增。
用特异性限制酶消化扩增片段以产生Nir启动子的5’端缺失，事先用AP2和Nir-23r-Sma引物扩增的片段经XmaI消化并将所得片段插入事先以XmaI消化的pBI201中，产生pNir3K-23。除了所用的下游引物分别是Nir51r-Sma、Nir103r-Sma和Nir158r-Sma之外，用相似策略产生pNir3K51、pNir3K103和pNir3K158质粒。插入事先以SmaI和BamHI消化过的pBI201中的AP2-Nir-23-Sma扩增片段用Smal-Bgl II消化，产生pNir2.2K-23。除了所用的下游引物分别是Nir51r-Sma、Nir103r-Sma和Nir158r-Sma之外，相同的策略用于产生pNir2.2K51、pNir2.2K 103和pNir2.2K158质粒。用限制性酶消化验证插入片段的忠实性和方向性。该缺失片段连到pBI201中GUS报告基因的5’末端，用于DNA轰击的瞬时表达研究。一旦鉴定足够的缺失片段，将它们亚克隆到二元植物表达载体例如pBI101(Clonetech)中。
为构建除NiR启动子外在GUS基因下游还包含NiR终止子的盒子，使用下述NiR特异性引物：
Nir2514c-Sac-5’AGAAGAGCTCAGTATATAGGTATTTGGTGA3’(SEQ ID NO：30)
Nir2728c-Sac-5’AGAAGAGCTCTTGTACATTTGGATAAGTCA3’(SEQ ID NO：31)
Nir3029r-Eco-5’AGAAGAATTCGTTTTCCCGATACTTCAACT3’(SEQ ID NO：32)
使用Nir2514c-Sac和Nir3029r-Eco引物PCR扩增出617bp的终止子片段。使用Nir2728c-Sac和Nir3029r-Eco引物PCR扩增出503bp的终止子片段。用SacI和EcoRI消化所得片段，并插入到已缺失了SacI与EcoRI位点间的NOS终止子的含有NiR-GUS构建体的质粒中。
按以下描述将该重组质粒用于通过根癌土壤杆菌感染的稳定整合。
土壤杆菌介导的DNA转移和转基因苜蓿系的产生
按照Khoudi等(1997，Gene，197：343-351)描述，用电穿孔将重组质粒导入根癌土壤杆菌株LBA4404。选出的土壤杆菌株在无选择压力(卡那霉素)下与基因型为C5-1的叶盘共培养4天。孵育后，清洗和营养叶片，再在B5H培养基上形成愈伤组织。愈伤组织再转移至SH培养基21天用于胚诱导，转移至BOi2Y培养基28天用于胚发育。从BOi2Y上取下鱼雷状的胚胎置于MS培养基以再生。除了共培养及MS上的再生，在所有培养基中都有卡那霉素。Desgages等对该方法有详细描述(1995，植物细胞组织器官培养42：129-140)。生根的小植株在温室中长到成熟。从基因组DNA用PCR扩增NiR-GUS片段以证实转移基因的整合。所用引物是：
Nir-102c-5’CACACTTCTTCACTCACCTCTCAA 3’(SEQ ID NO：25)
Nir-2016c-5’ATCTAGGAGGGGCAGACATTG 3’(SEQ ID NOS：26)
GUS228r-5’TCGGTATAAAGACTTCGCGCTGAT 3’(SEQ IDNOS：27)
土壤杆菌介导的DNA转移及转基因烟草品系的再生
按照Khoudi等(1997，Gene，197：343-351)描述用电穿孔将重组质粒导入根癌土壤杆菌株LBA4404。选择的株与叶盘在无卡那霉素的MS培养基上共培养2天。此后，外植体转移到选择性培养基(有卡那霉素的MS)。外植体放到培养基上3周使之由转染的细胞形成愈伤组织和苗。将卡那霉素抗性苗转移到发根MS培养基。发根的小植株在温室中长至成熟。从基因组DNA用PCR扩增NiR-GUS片段以证实转移基因的整合。所用引物是：
Nir-102c-5’CACACTTCTTCACTCACCTCTCAA 3’(SEQ ID NO：25)
Nir-2016c-5’ATCTAGGAGGGGCAGACATTG 3’(SEQ ID NOS：26)
GUS228r-5’TCGGTATAAAGACTTCGCGCTGAT 3’(SEQ ID NOS：27)
硝酸盐诱导
转基因的和未转基因的烟草和苜蓿植物在无硝酸盐的蛭石培养基上生长。通过反复加入无硝酸盐的Hoagland’s的溶液(Hoagland和Varmon，1950，Circular 347，California Agr.Exp.Stat.Berkeley)保持无机盐平衡。用浓度为5gL-1的20-20-20肥料或用补充了40mM硝酸盐的Hoagland’s的溶液浇灌植物进行硝酸盐的诱导。
烟草叶中的NiR启动子活性
在转录和翻译融合中GUS报告基因的上游放置NiR来源的启动子。本发明中NiR启动子5’缺失的分析在于：(1)包含编码区起始ATG上游2813bp的推定的全长启动子。(2)启动子的1905bp的版本，和(3)启动子更短的1111bp的版本。启动子的3’末端融合到GUS编码区的5’末端以形成转录和翻译融合体。所分析的翻译融合体允许产生β-葡糖醛酸糖苷酶，其包含(1)NiR叶绿体转运肽，(2)具有NiR的额外17个氨基酸的NiR转运肽，和(3)具有NiR的额外36个氨基酸的NiR转运肽。导入烟草植物中的NiR启动子的5’和3’缺失的12种组合如图1所示。
使用土壤杆菌介导的转染方法(Khoudi等，1997，Gene197：343-351)转移基因构建体到烟草植物。将转基因植物转移到生长室，并分析硝酸盐营养之前和之后其叶中β-葡糖醛酸糖苷酶含量。小植株第一片伸展的叶中测定的β-葡糖醛酸糖苷酶的平均水平如图1所示。
所有NiR来源的启动子显示对硝酸盐诱导的反应性。无论启动子截短与否，通常观察到β-葡糖醛酸糖苷酶的表达增加5-10倍，表明在起始ATG上游的前1.1kb中含有重要的硝酸盐应答元件。NiR启动子的5’和3’缺失都导致β-葡糖醛酸糖苷酶活性的重要改变。使用2.8kb启动子得到最高水平的GUS表达，表明远上游区域对叶中NiR的表达水平有调控作用。
启动子与GUS编码区的翻译性融合根据启动子5’末端的延伸之不同产生多种表达水平。然而，所有3种5’末端截短的最短的融合体(含有融合到β-葡糖醛酸糖苷酶氨基末端的17个氨基酸的NiR转运肽)都恒定地产生最高水平的活性。这种短的翻译融合，与上游启动子区域的最长延伸一起，导致最强的启动子(3kb+50)。当被诱导时，该特异性构建体产生的GUS表达水平比用35S-GUS-NOS构建体得到的多13倍。
当考虑启动子最长的5’延伸时，与GUS基因(3kb-5)转录融合的有效性比短的翻译融合(3kb+50)低7倍。然而在其诱导的状态下，在含有3kb-5启动子缺失的植物中，GUS表达水平比在35S-GUS-NOS植物中观察到的高1,8倍多。
总之，此处结果清楚表明了苜蓿NiR基因上游的序列能够驱动外源基因在烟草植物中高的和可诱导性的表达。
NiR终止子的有效性
用含有功能性定位的之启动子NiR和缺失(SEQ ID NOS：2，3，5，6)、35S，和3’UTR序列和终止子(SEQ ID NOS：15和16)的构建体转化烟草植物，以驱动报告基因GUS的转录与终止。如图1所示实验进行生长、硝酸盐诱导和GUS活性测定。结果如图2所示，证明Nir的终止子序列使得转录终止为可翻译的信使RNA。
苜蓿叶中NiR启动子活性
用Desgagnes等(1995，植物细胞组织器官培养42：129-140)的土壤杆菌介导的转染方法，得到图3所示的含有基因构建体的转基因苜蓿植物。体外将植物转移到生长室使其行正常营养性生长。每个转基因系的切条在蛭石上生长并用无硝酸盐的Hoagland培养基培养。两周后，用Nitragin(LiphaTech inc.，Milwaukee，WI)接种根。接种两周后，在根上形成根瘤。根瘤植物继续其营养性生长至少另一周，进行β-葡糖醛酸糖苷酶活性(诱导前)的荧光测定。测定后，用含有40mmolKN03的Hoagland培养基浇灌植物。诱导后两天，测定叶β-葡糖醛酸糖苷酶活性，以评估苜蓿叶中NiR启动子的硝酸盐诱导性。结果如图3所示。结果表明：当加入硝酸盐到根瘤苜蓿植物中时，NiR启动子诱导GUS报告基因的表达。总之，后一系列结果都证明了：当硝酸盐同化取代气态氮固定时，能够利用NiR启动子的可诱导性正调控苜蓿植物中外源基因的表达。
尽管本发明与其特定的实施方案一起被描述，应该理解，其能作进一步修改。本申请意在包括一般地参考本发明原则的任何改变、运用或调整，还包括在本发明所属领域内已知的或惯例的实践中对本发明的偏离，只要其中涉及了本发明以及应用了以上阐明的重要特性，和如下所附权利要求的范围。
序列表
<110>VEZINA，Louis-Philippe
D′AOUST，Marc-André
MEDICAGO INC
<120>调控外源基因转录的方法
<130>14149-3″PCT″
<150>US 60/157,133
<151>1999-10-04
<160>32
<170>FastSEQ for Windows Version 3.0
<210>1
<211>3714
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>1
ctgtacattc atcttgccgc ctttgcattc acttggccac aaagagtaga gagaaggaag 60
agaagagccc agacttcaag aagcgacctt gcaagtgcac tcgagggtca gaaactgtat 120
atcatatcta tgtgagagaa aggggaacat ttgagatgga gtccatttac ttgaggtata 180
cttattattt tgatcaataa atttgtatac ttcttattta gatcaataaa tttgtcatta 240
agctataatc caaaataaat tacgatcaaa tatgcaaatg ttagccagta cttgtgttaa 300
acttgatggc atctcttggt ttctttggca atcacatgcc taagaaataa atagtatcat 360
atgattgtgt ttggtcagac ttcagagtca gatgactctg tttggataaa cagcttaatt 420
aagcgcttat agaatatcat atgattgtgt ttggtcagac ttcagagcat ctcttggttt 480
ctctggcaat catatgccta agaaataaat agtatcatat gattgtgttt ggtcagactt 540
cagagtcaga tgaccctgtt tgggtaaaca gcttaattaa gtgcttatag aataagcgct 600
tatcatataa gtgcttttgt acagttattt ctatgaaagt agaagaaata gtcatattgt 660
tttaatataa gctatcctgg agagcttgtg gaaataacca gaaaagaact tatggacacg 720
tcatgagctg tttacataag atctccctaa cagtctcaaa agtgtttatg ccagtagata 780
aattcaaata agtcaatcta aacagaccct aaatccatta tggtacctat cattttagct 840
tattccatct ttattaagaa tgtcatgaga taacataatg ataacacatt attttgacac 900
aaatgggcag atctagcaat ttaactctgg agtccttcaa gactgctgtt cttacgaagt 960
tcacgtccct gaatcatgtt cctgtatgga agcctgaaag acctcaaatt ctaaaaggtg 1020
gcgataaatt gaaggtttac aaaatatacc ctgcgggctt gacacagagg caagctcttt 1080
ataccttcca gttcaacggg gatgttgatt tcagaagtca cttggagagc aatccttgtg 1140
ccaagtttga agtaattttt gtgtagcata tgttgagcta cctacaattt acatgatcac 1200
ctagcattag ctctttcact taactgagag aatgaagttt taggaatgag tatgaccatg 1260
gagtcggcat ggctttgtaa tgcctaccct actttggcca actcatcggg gatttacatt 1320
cagaaaatat acatgacttc aaccatactt aaaccccttt ttgtaagata actgaatgtt 1380
catatttaat gttgggttgt agtgttttta cttgattata tccagacagt tacaagttgg 1440
acaacaagat tgtgggtctg tactgttatt tatttatttt ttttttagca gaaacacctt 1500
atcttttgtt tcgtttgaat gtagaatgaa aataaaagaa agaaaatata acatcatcgg 1560
ccgcgcttgt ctaatttcgg gcagttagga tcctctccgg tcaccggaaa gtttcagtag 1620
aagaaacaaa acaccgtgac taaaatgata ctattatttt atttattgtg tttttctttt 1680
ttctaccgga actttttaga acggatccca actcgttccg gggccgctac aactgaaaca 1740
aaagaagata ttttctctct cttcagaaat gtaagttttc ctttacagat acccattcac 1800
catttgattc agatgtggtg actagagata aagcatacta atttgactct tggaaaccca 1860
taaagtttat gttatccgtg ttctggacca atccacttgg gggcataacc tgtgtctatg 1920
tgtggtttgg tttccattct gatttatgcg gcgacttgta atttaaaatc taggaggggc 1980
agacattgaa caatcccaat attttaataa cttatgcaag atttttttta ttaatgagat 2040
gatgtgtttg tgactgagat tgagtcatac atttcactaa gaaatggttc caagtaccaa 2100
actatcatga cccagttgca aacatgacgt tcgggagtgg tcactttgat agttcaattt 2160
catcttggct tcttattcct tttataattc taattcttct tgtgtaaact atttcatgta 2220
ttatttttct ttaaaattta catgtcattt attttgcctc actaactcaa ttttgcatat 2280
aacaatgata agtgatattt tgactcacaa aatttacatc aaatttcgac atcgtttatt 2340
atgttcattg gatgattaac aaatataaca aactttgcaa ctaattaacc accaactgaa 2400
tataattaac tataactgtg aaagtagtta accatatttt ttagatgtat atatcatccg 2460
ttgaatgtaa ttattcatat atttgaacta agttacccta caacttaaag aacttaaaga 2520
actcggtttg agacctgggg acgaaaatgt aatgagactt taatgttgac tttgacaccg 2580
caccacatgt gccttttaca tatagtttat atgacaagta atgacaatcc ttgctctatt 2640
ataaggcgac ccttagctcc aaccaaagga cgatggagtt aagaaagaaa ctcttgctta 2700
cttgtaaggt ccacacttct tcactcacct ctcaatttca tcctacaaaa atgtccaaac 2760
ttctctttct cacaatcaca aactcattcc aaacacactc tcttctccaa aaatgtcttc 2820
cttctcagta cgtttcctca ccccaccatc catctctcgt cccaacaaaa catggctact 2880
atctgctgca actccatcag ttgcacctgt ttcaacacca caagttgatg catcaaggtt 2940
ggagcctaga gttgaggaaa aagatggtta ctgggttttg aaggaagagt atagaggggg 3000
tattaatcct caggagaaag ttaagattca gaaagaacct atgaagcttt ttatggaagg 3060
tgggattaat gatttggcta atatgtctct tgaagagatt gaaagctcta agcttactaa 3120
agatgatatt gatgttagac ttaaatggct tggtcttttt catagaagga aacatcattg 3180
taagtttttt taccttcttt ttatacctca aagttctctc atactctgta tttgtttatt 3240
agtttttgta gacttaaata ttctctttga tttacatagt gaaactccat ttttgtttcc 3300
gaaattgtag tgtgtatagt ctagaaaatt aagaagtaga caaaatgatt tatgagattg 3360
taaattgtag gctttttatc aatttattaa ttttagagac caaaatttgc ctatcttatt 3420
tggaccaata ttgtatgtca ggatcgacat gagtttagta aaatcatgac ggcaccatga 3480
ctgtgttgaa gcttctttgt gtaactttaa ccaaaattat atggcacacc ataattatgc 3540
aaactcaccg tcgatccaaa catagaaatt cggtgttaat ctttgtgaga ataaaaagct 3600
atgagttatg ttgtactaat ttatttccat tgtgaaaatc agatggtaga tttatgatga 3660
gactgaaact tccaaatggg gtaacaacaa gtgctcaaac aagatacttg gcga       3714
<210>2
<211>2808
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>2
ctgtacattc atcttgccgc ctttgcattc acttggccac aaagagtaga gagaaggaag 60
agaagagccc agacttcaag aagcgacctt gcaagtgcac tcgagggtca gaaactgtat 120
atcatatcta tgtgagagaa aggggaacat ttgagatgga gtccatttac ttgaggtata 180
cttattattt tgatcaataa atttgtatac ttcttattta gatcaataaa tttgtcatta 240
agctataatc caaaataaat tacgatcaaa tatgcaaatg ttagccagta cttgtgttaa 300
acttgatggc atctcttggt ttctttggca atcacatgcc taagaaataa atagtatcat 360
atgattgtgt ttggtcagac ttcagagtca gatgactctg tttggataaa cagcttaatt 420
aagcgcttat agaatatcat atgattgtgt ttggtcagac ttcagagcat ctcttggttt 480
ctctggcaat catatgccta agaaataaat agtatcatat gattgtgttt ggtcagactt 540
cagagtcaga tgaccctgtt tgggtaaaca gcttaattaa gtgcttatag aataagcgct 600
tatcatataa gtgcttttgt acagttattt ctatgaaagt agaagaaata gtcatattgt 660
tttaatataa gctatcctgg agagcttgtg gaaataacca gaaaagaact tatggacacg 720
tcatgagctg tttacataag atctccctaa cagtctcaaa agtgtttatg ccagtagata 780
aattcaaata agtcaatcta aacagaccct aaatccatta tggtacctat cattttagct 840
tattccatct ttattaagaa tgtcatgaga taacataatg ataacacatt attttgacac 900
aaatgggcag atctagcaat ttaactctgg agtccttcaa gactgctgtt cttacgaagt 960
tcacgtccct gaatcatgtt cctgtatgga agcctgaaag acctcaaatt ctaaaaggtg 1020
gcgataaatt gaaggtttac aaaatatacc ctgcgggctt gacacagagg caagctcttt 1080
ataccttcca gttcaacggg gatgttgatt tcagaagtca cttggagagc aatccttgtg 1140
ccaagtttga agtaattttt gtgtagcata tgttgagcta cctacaattt acatgatcac 1200
ctagcattag ctctttcact taactgagag aatgaagttt taggaatgag tatgaccatg 1260
gagtcggcat ggctttgtaa tgcctaccct actttggcca actcatcggg gatttacatt 1320
cagaaaatat acatgacttc aaccatactt aaaccccttt ttgtaagata actgaatgtt 1380
catatttaat gttgggttgt agtgttttta cttgattata tccagacagt tacaagttgg 1440
acaacaagat tgtgggtctg tactgttatt tatttatttt ttttttagca gaaacacctt 1500
atcttttgtt tcgtttgaat gtagaatgaa aataaaagaa agaaaatata acatcatcgg 1560
ccgcgcttgt ctaatttcgg gcagttagga tcctctccgg tcaccggaaa gtttcagtag 1620
aagaaacaaa acaccgtgac taaaatgata ctattatttt atttattgtg tttttctttt 1680
ttctaccgga actttttaga acggatccca actcgttccg gggccgctac aactgaaaca 1740
aaagaagata ttttctctct cttcagaaat gtaagttttc ctttacagat acccattcac 1800
catttgattc agatgtggtg actagagata aagcatacta atttgactct tggaaaccca 1860
taaagtttat gttatccgtg ttctggacca atccacttgg gggcataacc tgtgtctatg 1920
tgtggtttgg tttccattct gatttatgcg gcgacttgta atttaaaatc taggaggggc 1980
agacattgaa caatcccaat attttaataa cttatgcaag atttttttta ttaatgagat 2040
gatgtgtttg tgactgagat tgagtcatac atttcactaa gaaatggttc caagtaccaa 2100
actatcatga cccagttgca aacatgacgt tcgggagtgg tcactttgat agttcaattt 2160
catcttggct tcttattcct tttataattc taattcttct tgtgtaaact atttcatgta 2220
ttatttttct ttaaaattta catgtcattt attttgcctc actaactcaa ttttgcatat 2280
aacaatgata agtgatattt tgactcacaa aatttacatc aaatttcgac atcgtttatt 2340
atgttcattg gatgattaac aaatataaca aactttgcaa ctaattaacc accaactgaa 2400
tataattaac tataactgtg aaagtagtta accatatttt ttagatgtat atatcatccg 2460
ttgaatgtaa ttattcatat atttgaacta agttacccta caacttaaag aacttaaaga 2520
actcggtttg agacctgggg acgaaaatgt aatgagactt taatgttgac tttgacaccg 2580
caccacatgt gccttttaca tatagtttat atgacaagta atgacaatcc ttgctctatt 2640
ataaggcgac ccttagctcc aaccaaagga cgatggagtt aagaaagaaa ctcttgctta 2700
cttgtaaggt ccacacttct tcactcacct ctcaatttca tcctacaaaa atgtccaaac 2760
ttctctttct cacaatcaca aactcattcc aaacacactc tcttctcc              2808
<210>3
<211>2069
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>3
gatctcccta acagtctcaa aagtgtttat gccagtagat aaattcaaat aagtcaatct 60
aaacagaccc taaatccatt atggtaccta tcattttagc ttattccatc tttattaaga 120
atgtcatgag ataacataat gataacacat tattttgaca caaatgggca gatctagcaa 180
tttaactctg gagtccttca agactgctgt tcttacgaag ttcacgtccc tgaatcatgt 240
tcctgtatgg aagcctgaaa gacctcaaat tctaaaaggt ggcgataaat tgaaggttta 300
caaaatatac cctgcgggct tgacacagag gcaagctctt tataccttcc agttcaacgg 360
ggatgttgat ttcagaagtc acttggagag caatccttgt gccaagtttg aagtaatttt 420
tgtgtagcat atgttgagct acctacaatt tacatgatca cctagcatta gctctttcac 480
ttaactgaga gaatgaagtt ttaggaatga gtatgaccat ggagtcggca tggctttgta 540
atgcctaccc tactttggcc aactcatcgg ggatttacat tcagaaaata tacatgactt 600
caaccatact taaacccctt tttgtaagat aactgaatgt tcatatttaa tgttgggttg 660
tagtgttttt acttgattat atccagacag ttacaagttg gacaacaaga ttgtgggtct 720
gtactgttat ttatttattt tttttttagc agaaacacct tatcttttgt ttcgtttgaa 780
tgtagaatga aaataaaaga aagaaaatat aacatcatcg gccgcgcttg tctaatttcg 840
ggcagttagg atcctctccg gtcaccggaa agtttcagta gaagaaacaa aacaccgtga 900
ctaaaatgat actattattt tatttattgt gtttttcttt tttctaccgg aactttttag 960
aacggatccc aactcgttcc ggggccgcta caactgaaac aaaagaagat attttctctc 1020
tcttcagaaa tgtaagtttt cctttacaga tacccattca ccatttgatt cagatgtggt 1080
gactagagat aaagcatact aatttgactc ttggaaaccc ataaagttta tgttatccgt 1140
gttctggacc aatccacttg ggggcataac ctgtgtctat gtgtggtttg gtttccattc 1200
tgatttatgc ggcgacttgt aatttaaaat ctaggagggg cagacattga acaatcccaa 1260
tattttaata acttatgcaa gatttttttt attaatgaga tgatgtgttt gtgactgaga 1320
ttgagtcata catttcacta agaaatggtt ccaagtacca aactatcatg acccagttgc 1380
aaacatgacg ttcgggagtg gtcactttga tagttcaatt tcatcttggc ttcttattcc 1440
ttttataatt ctaattcttc ttgtgtaaac tatttcatgt attatttttc tttaaaattt 1500
acatgtcatt tattttgcct cactaactca attttgcata taacaatgat aagtgatatt 1560
ttgactcaca aaatttacat caaatttcga catcgtttat tatgttcatt ggatgattaa 1620
caaatataac aaactttgca actaattaac caccaactga atataattaa ctataactgt 1680
gaaagtagtt aaccatattt tttagatgta tatatcatcc gttgaatgta attattcata 1740
tatttgaact aagttaccct acaacttaaa gaacttaaag aactcggttt gagacctggg 1800
gacgaaaatg taatgagact ttaatgttga ctttgacacc gcaccacatg tgccttttac 1860
atatagttta tatgacaagt aatgacaatc cttgctctat tataaggcga cccttagctc 1920
caaccaaagg acgatggagt taagaaagaa actcttgctt acttgtaagg tccacacttc 1980
ttcactcacc tctcaatttc atcctacaaa aatgtccaaa cttctctttc tcacaatcac 2040
aaactcattc caaacacact ctcttctcc                                   2069
<210>4
<211>1220
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>4
gatcctctcc ggtcaccgga aagtttcagt agaagaaaca aaacaccgtg actaaaatga 60
tactattatt ttatttattg tgtttttctt ttttctaccg gaacttttta gaacggatcc 120
caactcgttc cggggccgct acaactgaaa caaaagaaga tattttctct ctcttcagaa 180
atgtaagttt tcctttacag atacccattc accatttgat tcagatgtgg tgactagaga 240
taaagcatac taatttgact cttggaaacc cataaagttt atgttatccg tgttctggac 300
caatccactt gggggcataa cctgtgtcta tgtgtggttt ggtttccatt ctgatttatg 360
cggcgacttg taatttaaaa tctaggaggg gcagacattg aacaatccca atattttaat 420
aacttatgca agattttttt tattaatgag atgatgtgtt tgtgactgag attgagtcat 480
acatttcact aagaaatggt tccaagtacc aaactatcat gacccagttg caaacatgac 540
gttcgggagt ggtcactttg atagttcaat ttcatcttgg cttcttattc cttttataat 600
tctaattctt cttgtgtaaa ctatttcatg tattattttt ctttaaaatt tacatgtcat 660
ttattttgcc tcactaactc aattttgcat ataacaatga taagtgatat tttgactcac 720
aaaatttaca tcaaatttcg acatcgttta ttatgttcat tggatgatta acaaatataa 780
caaactttgc aactaattaa ccaccaactg aatataatta actataactg tgaaagtagt 840
taaccatatt ttttagatgt atatatcatc cgttgaatgt aattattcat atatttgaac 900
taagttaccc tacaacttaa agaacttaaa gaactcggtt tgagacctgg ggacgaaaat 960
gtaatgagac tttaatgttg actttgacac cgcaccacat gtgcctttta catatagttt 1020
atatgacaag taatgacaat ccttgctcta ttataaggcg acccttagct ccaaccaaag 1080
gacgatggag ttaagaaaga aactcttgct tacttgtaag gtccacactt cttcactcac 1140
ctctcaattt catcctacaa aaatgtccaa acttctcttt ctcacaatca caaactcatt 1200
ccaaacacac tctcttctcc                                             1220
<210>5
<211>2863
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>5
ctgtacattc atcttgccgc ctttgcattc acttggccac aaagagtaga gagaaggaag 60
agaagagccc agacttcaag aagcgacctt gcaagtgcac tcgagggtca gaaactgtat 120
atcatatcta tgtgagagaa aggggaacat ttgagatgga gtccatttac ttgaggtata 180
cttattattt tgatcaataa atttgtatac ttcttattta gatcaataaa tttgtcatta 240
agctataatc caaaataaat tacgatcaaa tatgcaaatg ttagccagta cttgtgttaa 300
acttgatggc atctcttggt ttctttggca atcacatgcc taagaaataa atagtatcat 360
atgattgtgt ttggtcagac ttcagagtca gatgactctg tttggataaa cagcttaatt 420
aagcgcttat agaatatcat atgattgtgt ttggtcagac ttcagagcat ctcttggttt 480
ctctggcaat catatgccta agaaataaat agtatcatat gattgtgttt ggtcagactt 540
cagagtcaga tgaccctgtt tgggtaaaca gcttaattaa gtgcttatag aataagcgct 600
tatcatataa gtgcttttgt acagttattt ctatgaaagt agaagaaata gtcatattgt 660
tttaatataa gctatcctgg agagcttgtg gaaataacca gaaaagaact tatggacacg 720
tcatgagctg tttacataag atctccctaa cagtctcaaa agtgtttatg ccagtagata 780
aattcaaata agtcaatcta aacagaccct aaatccatta tggtacctat cattttagct 840
tattccatct ttattaagaa tgtcatgaga taacataatg ataacacatt attttgacac 900
aaatgggcag atctagcaat ttaactctgg agtccttcaa gactgctgtt cttacgaagt 960
tcacgtccct gaatcatgtt cctgtatgga agcctgaaag acctcaaatt ctaaaaggtg 1020
gcgataaatt gaaggtttac aaaatatacc ctgcgggctt gacacagagg caagctcttt 1080
ataccttcca gttcaacggg gatgttgatt tcagaagtca cttggagagc aatccttgtg 1140
ccaagtttga agtaattttt gtgtagcata tgttgagcta cctacaattt acatgatcac 1200
ctagcattag ctctttcact taactgagag aatgaagttt taggaatgag tatgaccatg 1260
gagtcggcat ggctttgtaa tgcctaccct actttggcca actcatcggg gatttacatt 1320
cagaaaatat acatgacttc aaccatactt aaaccccttt ttgtaagata actgaatgtt 1380
catatttaat gttgggttgt agtgttttta cttgattata tccagacagt tacaagttgg 1440
acaacaagat tgtgggtctg tactgttatt tatttatttt ttttttagca gaaacacctt 1500
atcttttgtt tcgtttgaat gtagaatgaa aataaaagaa agaaaatata acatcatcgg 1560
ccgcgcttgt ctaatttcgg gcagttagga tcctctccgg tcaccggaaa gtttcagtag 1620
aagaaacaaa acaccgtgac taaaatgata ctattatttt atttattgtg tttttctttt 1680
ttctaccgga actttttaga acggatccca actcgttccg gggccgctac aactgaaaca 1740
aaagaagata ttttctctct cttcagaaat gtaagttttc ctttacagat acccattcac 1800
catttgattc agatgtggtg actagagata aagcatacta atttgactct tggaaaccca 1860
taaagtttat gttatccgtg ttctggacca atccacttgg gggcataacc tgtgtctatg 1920
tgtggtttgg tttccattct gatttatgcg gcgacttgta atttaaaatc taggaggggc 1980
agacattgaa caatcccaat attttaataa cttatgcaag atttttttta ttaatgagat 2040
gatgtgtttg tgactgagat tgagtcatac atttcactaa gaaatggttc caagtaccaa 2100
actatcatga cccagttgca aacatgacgt tcgggagtgg tcactttgat agttcaattt 2160
catcttggct tcttattcct tttataattc taattcttct tgtgtaaact atttcatgta 2220
ttatttttct ttaaaattta catgtcattt attttgcctc actaactcaa ttttgcatat 2280
aacaatgata agtgatattt tgactcacaa aatttacatc aaatttcgac atcgtttatt 2340
atgttcattg gatgattaac aaatataaca aactttgcaa ctaattaacc accaactgaa 2400
tataattaac tataactgtg aaagtagtta accatatttt ttagatgtat atatcatccg 2460
ttgaatgtaa ttattcatat atttgaacta agttacccta caacttaaag aacttaaaga 2520
actcggtttg agacctgggg acgaaaatgt aatgagactt taatgttgac tttgacaccg 2580
caccacatgt gccttttaca tatagtttat atgacaagta atgacaatcc ttgctctatt 2640
ataaggcgac ccttagctcc aaccaaagga cgatggagtt aagaaagaaa ctcttgctta 2700
cttgtaaggt ccacacttct tcactcacct ctcaatttca tcctacaaaa atgtccaaac 2760
ttctctttct cacaatcaca aactcattcc aaacacactc tcttctccaa aaatgtcttc 2820
cttctcagta cgtttcctca ccccaccatc catctctcgt ccc                   2863
<210>6
<211>2124
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>6
gatctcccta acagtctcaa aagtgtttat gccagtagat aaattcaaat aagtcaatct 60
aaacagaccc taaatccatt atggtaccta tcattttagc ttattccatc tttattaaga 120
atgtcatgag ataacataat gataacacat tattttgaca caaatgggca gatctagcaa 180
tttaactctg gagtccttca agactgctgt tcttacgaag ttcacgtccc tgaatcatgt 240
tcctgtatgg aagcctgaaa gacctcaaat tctaaaaggt ggcgataaat tgaaggttta 300
caaaatatac cctgcgggct tgacacagag gcaagctctt tataccttcc agttcaacgg 360
ggatgttgat ttcagaagtc acttggagag caatccttgt gccaagtttg aagtaatttt 420
tgtgtagcat atgttgagct acctacaatt tacatgatca cctagcatta gctctttcac 480
ttaactgaga gaatgaagtt ttaggaatga gtatgaccat ggagtcggca tggctttgta 540
atgcctaccc tactttggcc aactcatcgg ggatttacat tcagaaaata tacatgactt 600
caaccatact taaacccctt tttgtaagat aactgaatgt tcatatttaa tgttgggttg 660
tagtgttttt acttgattat atccagacag ttacaagttg gacaacaaga ttgtgggtct 720
gtactgttat ttatttattt tttttttagc agaaacacct tatcttttgt ttcgtttgaa 780
tgtagaatga aaataaaaga aagaaaatat aacatcatcg gccgcgcttg tctaatttcg 840
ggcagttagg atcctctccg gtcaccggaa agtttcagta gaagaaacaa aacaccgtga 900
ctaaaatgat actattattt tatttattgt gtttttcttt tttctaccgg aactttttag 960
aacggatccc aactcgttcc ggggccgcta caactgaaac aaaagaagat attttctctc 1020
tcttcagaaa tgtaagtttt cctttacaga tacccattca ccatttgatt cagatgtggt 1080
gactagagat aaagcatact aatttgactc ttggaaaccc ataaagttta tgttatccgt 1140
gttctggacc aatccacttg ggggcataac ctgtgtctat gtgtggtttg gtttccattc 1200
tgatttatgc ggcgacttgt aatttaaaat ctaggagggg cagacattga acaatcccaa 1260
tattttaata acttatgcaa gatttttttt attaatgaga tgatgtgttt gtgactgaga 1320
ttgagtcata catttcacta agaaatggtt ccaagtacca aactatcatg acccagttgc 1380
aaacatgacg ttcgggagtg gtcactttga tagttcaatt tcatcttggc ttcttattcc 1440
ttttataatt ctaattcttc ttgtgtaaac tatttcatgt attatttttc tttaaaattt 1500
acatgtcatt tattttgcct cactaactca attttgcata taacaatgat aagtgatatt 1560
ttgactcaca aaatttacat caaatttcga catcgtttat tatgttcatt ggatgattaa 1620
caaatataac aaactttgca actaattaac caccaactga atataattaa ctataactgt 1680
gaaagtagtt aaccatattt tttagatgta tatatcatcc gttgaatgta attattcata 1740
tatttgaact aagttaccct acaacttaaa gaacttaaag aactcggttt gagacctggg 1800
gacgaaaatg taatgagact ttaatgttga ctttgacacc gcaccacatg tgccttttac 1860
atatagttta tatgacaagt aatgacaatc cttgctctat tataaggcga cccttagctc 1920
caaccaaagg acgatggagt taagaaagaa actcttgctt acttgtaagg tccacacttc 1980
ttcactcacc tctcaatttc atcctacaaa aatgtccaaa cttctctttc tcacaatcac 2040
aaactcattc caaacacact ctcttctcca aaaatgtctt ccttctcagt acgtttcctc 2100
accccaccat ccatctctcg tccc                                        2124
<210>7
<211>1160
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>7
gatcccaact cgttccgggg ccgctacaac tgaaacaaaa gaagatattt tctctctctt 60
cagaaatgta agttttcctt tacagatacc cattcaccat ttgattcaga tgtggtgact 120
agagataaag catactaatt tgactcttgg aaacccataa agtttatgtt atccgtgttc 180
tggaccaatc cacttggggg cataacctgt gtctatgtgt ggtttggttt ccattctgat 240
ttatgcggcg acttgtaatt taaaatctag gaggggcaga cattgaacaa tcccaatatt 300
ttaataactt atgcaagatt ttttttatta atgagatgat gtgtttgtga ctgagattga 360
gtcatacatt tcactaagaa atggttccaa gtaccaaact atcatgaccc agttgcaaac 420
atgacgttcg ggagtggtca ctttgatagt tcaatttcat cttggcttct tattcctttt 480
ataattctaa ttcttcttgt gtaaactatt tcatgtatta tttttcttta aaatttacat 540
gtcatttatt ttgcctcact aactcaattt tgcatataac aatgataagt gatattttga 600
ctcacaaaat ttacatcaaa tttcgacatc gtttattatg ttcattggat gattaacaaa 660
tataacaaac tttgcaacta attaaccacc aactgaatat aattaactat aactgtgaaa 720
gtagttaacc atatttttta gatgtatata tcatccgttg aatgtaatta ttcatatatt 780
tgaactaagt taccctacaa cttaaagaac ttaaagaact cggtttgaga cctggggacg 840
aaaatgtaat gagactttaa tgttgacttt gacaccgcac cacatgtgcc ttttacatat 900
agtttatatg acaagtaatg acaatccttg ctctattata aggcgaccct tagctccaac 960
caaaggacga tggagttaag aaagaaactc ttgcttactt gtaaggtcca cacttcttca 1020
ctcacctctc aatttcatcc tacaaaaatg tccaaacttc tctttctcac aatcacaaac 1080
tcattccaaa cacactctct tctccaaaaa tgtcttcctt ctcagtacgt ttcctcaccc 1140
caccatccat ctctcgtccc                                             1160
<210>8
<211>2904
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>8
ctgtacattc atcttgccgc ctttgcattc acttggccac aaagagtaga gagaaggaag 60
agaagagccc agacttcaag aagcgacctt gcaagtgcac tcgagggtca gaaactgtat 120
atcatatcta tgtgagagaa aggggaacat ttgagatgga gtccatttac ttgaggtata 180
cttattattt tgatcaataa atttgtatac ttcttattta gatcaataaa tttgtcatta 240
agctataatc caaaataaat tacgatcaaa tatgcaaatg ttagccagta cttgtgttaa 300
acttgatggc atctcttggt ttctttggca atcacatgcc taagaaataa atagtatcat 360
atgattgtgt ttggtcagac ttcagagtca gatgactctg tttggataaa cagcttaatt 420
aagcgcttat agaatatcat atgattgtgt ttggtcagac ttcagagcat ctcttggttt 480
ctctggcaat catatgccta agaaataaat agtatcatat gattgtgttt ggtcagactt 540
cagagtcaga tgaccctgtt tgggtaaaca gcttaattaa gtgcttatag aataagcgct 600
tatcatataa gtgcttttgt acagttattt ctatgaaagt agaagaaata gtcatattgt 660
tttaatataa gctatcctgg agagcttgtg gaaataacca gaaaagaact tatggacacg 720
tcatgagctg tttacataag atctccctaa cagtctcaaa agtgtttatg ccagtagata 780
aattcaaata agtcaatcta aacagaccct aaatccatta tggtacctat cattttagct 840
tattccatct ttattaagaa tgtcatgaga taacataatg ataacacatt attttgacac 900
aaatgggcag atctagcaat ttaactctgg agtccttcaa gactgctgtt cttacgaagt 960
tcacgtccct gaatcatgtt cctgtatgga agcctgaaag acctcaaatt ctaaaaggtg 1020
gcgataaatt gaaggtttac aaaatatacc ctgcgggctt gacacagagg caagctcttt 1080
ataccttcca gttcaacggg gatgttgatt tcagaagtca cttggagagc aatccttgtg 1140
ccaagtttga agtaattttt gtgtagcata tgttgagcta cctacaattt acatgatcac 1200
ctagcattag ctctttcact taactgagag aatgaagttt taggaatgag tatgaccatg 1260
gagtcggcat ggctttgtaa tgcctaccct actttggcca actcatcggg gatttacatt 1320
cagaaaatat acatgacttc aaccatactt aaaccccttt ttgtaagata actgaatgtt 1380
catatttaat gttgggttgt agtgttttta cttgattata tccagacagt tacaagttgg 1440
acaacaagat tgtgggtctg tactgttatt tatttatttt ttttttagca gaaacacctt 1500
atcttttgtt tcgtttgaat gtagaatgaa aataaaagaa agaaaatata acatcatcgg 1560
ccgcgcttgt ctaatttcgg gcagttagga tcctctccgg tcaccggaaa gtttcagtag 1620
aagaaacaaa acaccgtgac taaaatgata ctattatttt atttattgtg tttttctttt 1680
ttctaccgga actttttaga acggatccca actcgttccg gggccgctac aactgaaaca 1740
aaagaagata ttttctctct cttcagaaat gtaagttttc ctttacagat acccattcac 1800
catttgattc agatgtggtg actagagata aagcatacta atttgactct tggaaaccca 1860
taaagtttat gttatccgtg ttctggacca atccacttgg gggcataacc tgtgtctatg 1920
tgtggtttgg tttccattct gatttatgcg gcgacttgta atttaaaatc taggaggggc 1980
agacattgaa caatcccaat attttaataa cttatgcaag atttttttta ttaatgagat 2040
gatgtgtttg tgactgagatt gagtcatac atttcactaa gaaatggttc caagtaccaa 2100
actatcatga cccagttgca aacatgacgt tcgggagtgg tcactttgat agttcaattt 2160
catcttggct tcttattcct tttataattc taattcttct tgtgtaaact atttcatgta 2220
ttatttttct ttaaaattta catgtcattt attttgcctc actaactcaa ttttgcatat 2280
aacaatgata agtgatattt tgactcacaa aatttacatc aaatttcgac atcgtttatt 2340
atgttcattg gatgattaac aaatataaca aactttgcaa ctaattaacc accaactgaa 2400
tataattaac tataactgtg aaagtagtta accatatttt ttagatgtat atatcatccg 2460
ttgaatgtaa ttattcatat atttgaacta agttacccta caacttaaag aacttaaaga 2520
actcggtttg agacctgggg acgaaaatgt aatgagactt taatgttgac tttgacaccg 2580
caccacatgt gccttttaca tatagtttat atgacaagta atgacaatcc ttgctctatt 2640
ataaggcgac ccttagctcc aaccaaagga cgatggagtt aagaaagaaa ctcttgctta 2700
cttgtaaggt ccacacttct tcactcacct ctcaatttca tcctacaaaa atgtccaaac 2760
ttctctttct cacaatcaca aactcattcc aaacacactc tcttctccaa aaatgtcttc    2820
cttctcagta cgtttcctca ccccaccatc catctctcgt cccaacaaaa catggctact    2880
atctgctgca actccatcag ttgc    2904
<210>9
<211>2165
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>9
gatctcccta acagtctcaa aagtgtttat gccagtagat aaattcaaat aagtcaatct 60
aaacagaccc taaatccatt atggtaccta tcattttagc ttattccatc tttattaaga 120
atgtcatgag ataacataat gataacacat tattttgaca caaatgggca gatctagcaa 180
tttaactctg gagtccttca agactgctgt tcttacgaag ttcacgtccc tgaatcatgt 240
tcctgtatgg aagcctgaaa gacctcaaat tctaaaaggt ggcgataaat tgaaggttta 300
caaaatatac cctgcgggct tgacacagag gcaagctctt tataccttcc agttcaacgg 360
ggatgttgat ttcagaagtc acttggagag caatccttgt gccaagtttg aagtaatttt 420
tgtgtagcat atgttgagct acctacaatt tacatgatca cctagcatta gctctttcac 480
ttaactgaga gaatgaagtt ttaggaatga gtatgaccat ggagtcggca tggctttgta 540
atgcctaccc tactttggcc aactcatcgg ggatttacat tcagaaaata tacatgactt 600
caaccatact taaacccctt tttgtaagat aactgaatgt tcatatttaa tgttgggttg 660
tagtgttttt acttgattat atccagacag ttacaagttg gacaacaaga ttgtgggtct 720
gtactgttat ttatttattt tttttttagc agaaacacct tatcttttgt ttcgtttgaa 780
tgtagaatga aaataaaaga aagaaaatat aacatcatcg gccgcgcttg tctaatttcg 840
ggcagttagg atcctctccg gtcaccggaa agtttcagta gaagaaacaa aacaccgtga 900
ctaaaatgat actattattt tatttattgt gtttttcttt tttctaccgg aactttttag 960
aacggatccc aactcgttcc ggggccgcta caactgaaac aaaagaagat attttctctc 1020
tcttcagaaa tgtaagtttt cctttacaga tacccattca ccatttgatt cagatgtggt 1080
gactagagat aaagcatact aatttgactc ttggaaaccc ataaagttta tgttatccgt 1140
gttctggacc aatccacttg ggggcataac ctgtgtctat gtgtggtttg gtttccattc 1200
tgatttatgc ggcgacttgt aatttaaaat ctaggagggg cagacattga acaatcccaa 1260
tattttaata acttatgcaa gatttttttt attaatgaga tgatgtgttt gtgactgaga 1320
ttgagtcata catttcacta agaaatggtt ccaagtacca aactatcatg acccagttgc 1380
aaacatgacg ttcgggagtg gtcactttga tagttcaatt tcatcttggc ttcttattcc 1440
ttttataatt ctaattcttc ttgtgtaaAc tatttcatgt attatttttc tttaaaattt 1500
acatgtcatt tattttgcct cactaactca attttgcata taacaatgat aagtgatatt 1560
ttgactcaca aaatttacat caaatttcga catcgtttat tatgttcatt ggatgattaa 1620
caaatataac aaactttgca actaattaac caccaactga atataattaa ctataactgt 1680
gaaagtagtt aaccatattt tttagatgta tatatcatcc gttgaatgta attattcata 1740
tatttgaact aagttaccct acaacttaaa gaacttaaag aactcggttt gagacctggg 1800
gacgaaaatg taatgagact ttaatgttga ctttgacacc gcaccacatg tgccttttac 1860
atatagttta tatgacaagt aatgacaatc cttgctctat tataaggcga cccttagctc 1920
caaccaaagg acgatggagt taagaaagaa actcttgctt acttgtaagg tccacacttc 1980
ttcactcacc tctcaatttc atcctacaaa aatgtccaaa cttctctttc tcacaatcac 2040
aaactcattc caaacacact ctcttctcca aaaatgtctt ccttctcagt acgtttcctc 2100
accccaccat ccatctctcg tcccaacaaa acatggctac tatctgctgc aactccatca 2160
gttgc                                                             2165
<210>10
<211>1316
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>10
gatcctctcc ggtcaccgga aagtttcagt agaagaaaca aaacaccgtg actaaaatga 60
tactattatt ttatttattg tgtttttctt ttttctaccg gaacttttta gaacggatcc 120
caactcgttc cggggccgct acaactgaaa caaaagaaga tattttctct ctcttcagaa 180
atgtaagttt tcctttacag atacccattc accatttgat tcagatgtgg tgactagaga 240
taaagcatac taatttgact cttggaaacc cataaagttt atgttatccg tgttctggac 300
caatccactt gggggcataa cctgtgtcta tgtgtggttt ggtttccatt ctgatttatg 360
cggcgacttg taatttaaaa tctaggaggg gcagacattg aacaatccca atattttaat 420
aacttatgca agattttttt tattaatgag atgatgtgtt tgtgactgag attgagtcat 480
acatttcact aagaaatggt tccaagtacc aaactatcat gacccagttg caaacatgac 540
gttcgggagt ggtcactttg atagttcaat ttcatcttgg cttcttattc cttttataat 600
tctaattctt cttgtgtaaa ctatttcatg tattattttt ctttaaaatt tacatgtcat 660
ttattttgcc tcactaactc aattttgcat ataacaatga taagtgatat tttgactcac 720
aaaatttaca tcaaatttcg acatcgttta ttatgttcat tggatgatta acaaatataa 780
caaactttgc aactaattaa ccaccaactg aatataatta actataactg tgaaagtagt 840
taaccatatt ttttagatgt atatatcatc cgttgaatgt aattattcat atatttgaac 900
taagttaccc tacaacttaa agaacttaaa gaactcggtt tgagacctgg ggacgaaaat 960
gtaatgagac tttaatgttg actttgacac cgcaccacat gtgcctttta catatagttt 1020
atatgacaag taatgacaat ccttgctcta ttataaggcg acccttagct ccaaccaaag 1080
gacgatggag ttaagaaaga aactcttgct tacttgtaag gtccacactt cttcactcac 1140
ctctcaattt catcctacaa aaatgtccaa acttctcttt ctcacaatca caaactcatt 1200
ccaaacacac tctcttctcc aaaaatgtct tccttctcag tacgtttcct caccccacca 1260
tccatctctc gtcccaacaa aacatggcta ctatctgctg caactccatc agttgc     1316
<210>11
<211>2971
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>11
ctgtacattc atcttgccgc ctttgcattc acttggccac aaagagtaga gagaaggaag 60
agaagagccc agacttcaag aagcgacctt gcaagtgcac tcgagggtca gaaactgtat 120
atcatatcta tgtgagagaa aggggaacat ttgagatgga gtccatttac ttgaggtata 180
cttattattt tgatcaataa atttgtatac ttcttattta gatcaataaa tttgtcatta 240
agctataatc caaaataaat tacgatcaaa tatgcaaatg ttagccagta cttgtgttaa 300
acttgatggc atctcttggt ttctttggca atcacatgcc taagaaataa atagtatcat 360
atgattgtgt ttggtcagac ttcagagtca gatgactctg tttggataaa cagcttaatt 420
aagcgcttat agaatatcat atgattgtgt ttggtcagac ttcagagcat ctcttggttt 480
ctctggcaat catatgccta agaaataaat agtatcatat gattgtgttt ggtcagactt 540
cagagtcaga tgaccctgtt tgggtaaaca gcttaattaa gtgcttatag aataagcgct 600
tatcatataa gtgcttttgt acagttattt ctatgaaagt agaagaaata gtcatattgt 660
tttaatataa gctatcctgg agagcttgtg gaaataacca gaaaagaact tatggacacg 720
tcatgagctg tttacataag atctccctaa cagtctcaaa agtgtttatg ccagtagata 780
aattcaaata agtcaatcta aacagaccct aaatccatta tggtacctat cattttagct 840
tattccatct ttattaagaa tgtcatgaga taacataatg ataacacatt attttgacac 900
aaatgggcag atctagcaat ttaactctgg agtccttcaa gactgctgtt cttacgaagt 960
tcacgtccct gaatcatgtt cctgtatgga agcctgaaag acctcaaatt ctaaaaggtg 1020
gcgataaatt gaaggtttac aaaatatacc ctgcgggctt gacacagagg caagctcttt 1080
ataccttcca gttcaacggg gatgttgatt tcagaagtca cttggagagc aatccttgtg 1140
ccaagtttga agtaattttt gtgtagcata tgttgagcta cctacaattt acatgatcac 1200
ctagcattag ctctttcact taactgagag aatgaagttt taggaatgag tatgaccatg 1260
gagtcggcat ggctttgtaa tgcctaccct actttggcca actcatcggg gatttacatt 1320
cagaaaatat acatgacttc aaccatactt aaaccccttt ttgtaagata actgaatgtt 1380
catatttaat gttgggttgt agtgttttta cttgattata tccagacagt tacaagttgg 1440
acaacaagat tgtgggtctg tactgttatt tatttatttt ttttttagca gaaacacctt 1500
atcttttgtt tcgtttgaat gtagaatgaa aataaaagaa agaaaatata acatcatcgg 1560
ccgcgcttgt ctaatttcgg gcagttagga tcctctccgg tcaccggaaa gtttcagtag 1620
aagaaacaaa acaccgtgac taaaatgata ctattatttt atttattgtg tttttctttt 1680
ttctaccgga actttttaga acggatccca actcgttccg gggccgctac aactgaaaca 1740
aaagaagata ttttctctct cttcagaaat gtaagttttc ctttacagat acccattcac 1800
catttgattc agatgtggtg actagagata aagcatacta atttgactct tggaaaccca 1860
taaagtttat gttatccgtg ttctggacca atccacttgg gggcataacc tgtgtctatg 1920
tgtggtttgg tttccattct gatttatgcg gcgacttgta atttaaaatc taggaggggc 1980
agacattgaa caatcccaat attttaataa cttatgcaag atttttttta ttaatgagat 2040
gatgtgtttg tgactgagat tgagtcatac atttcactaa gaaatggttc caagtaccaa 2100
actatcatga cccagttgca aacatgacgt tcgggagtgg tcactttgat agttcaattt 2160
catcttggct tcttattcct tttataattc taattcttct tgtgtaaact atttcatgta 2220
ttatttttct ttaaaattta catgtcattt attttgcctc actaactcaa ttttgcatat 2280
aacaatgata agtgatattt tgactcacaa aatttacatc aaatttcgac atcgtttatt 2340
atgttcattg gatgattaac aaatataaca aactttgcaa ctaattaacc accaactgaa 2400
tataattaac tataactgtg aaagtagtta accatatttt ttagatgtat atatcatccg 2460
ttgaatgtaa ttattcatat atttgaacta agttacccta caacttaaag aacttaaaga 2520
actcggtttg agacctgggg acgaaaatgt aatgagactt taatgttgac tttgacaccg 2580
caccacatgt gccttttaca tatagtttat atgacaagta atgacaatcc ttgctctatt 2640
ataaggcgac ccttagctcc aaccaaagga cgatggagtt aagaaagaaa ctcttgctta 2700
cttgtaaggt ccacacttct tcactcacct ctcaatttca tcctacaaaa atgtccaaac 2760
ttctctttct cacaatcaca aactcattcc aaacacactc tcttctccaa aaatgtcttc 2820
cttctcagta cgtttcctca ccccaccatc catctctcgt cccaacaaaa catggctact 2880
atctgctgca actccatcag ttgcacctgt ttcaacacca caagttgatg catcaaggtt 2940
ggagcctaga gttgaggaaa aagatggtta c                                2971
<210>12
<211>2232
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>12
gatctcccta acagtctcaa aagtgtttat gccagtagat aaattcaaat aagtcaatct 60
aaacagaccc taaatccatt atggtaccta tcattttagc ttattccatc tttattaaga 120
atgtcatgag ataacataat gataacacat tattttgaca caaatgggca gatctagcaa 180
tttaactctg gagtccttca agactgctgt tcttacgaag ttcacgtccc tgaatcatgt 240
tcctgtatgg aagcctgaaa gacctcaaat tctaaaaggt ggcgataaat tgaaggttta 300
caaaatatac cctgcgggct tgacacagag gcaagctctt tataccttcc agttcaacgg 360
ggatgttgat ttcagaagtc acttggagag caatccttgt gccaagtttg aagtaatttt 420
tgtgtagcat atgttgagct acctacaatt tacatgatca cctagcatta gctctttcac 480
ttaactgaga gaatgaagtt ttaggaatga gtatgaccat ggagtcggca tggctttgta 540
atgcctaccc tactttggcc aactcatcgg ggatttacat tcagaaaata tacatgactt 600
caaccatact taaacccctt tttgtaagat aactgaatgt tcatatttaa tgttgggttg 660
tagtgttttt acttgattat atccagacag ttacaagttg gacaacaaga ttgtgggtct 720
gtactgttat ttatttattt tttttttagc agaaacacct tatcttttgt ttcgtttgaa 780
tgtagaatga aaataaaaga aagaaaatat aacatcatcg gccgcgcttg tctaatttcg 840
ggcagttagg atcctctccg gtcaccggaa agtttcagta gaagaaacaa aacaccgtga 900
ctaaaatgat actattattt tatttattgt gtttttcttt tttctaccgg aactttttag 960
aacggatccc aactcgttcc ggggccgcta caactgaaac aaaagaagat attttctctc 1020
tcttcagaaa tgtaagtttt cctttacaga tacccattca ccatttgatt cagatgtggt 1080
gactagagat aaagcatact aatttgactc ttggaaaccc ataaagttta tgttatccgt 1140
gttctggacc aatccacttg ggggcataac ctgtgtctat gtgtggtttg gtttccattc 1200
tgatttatgc ggcgacttgt aatttaaaat ctaggagggg cagacattga acaatcccaa 1260
tattttaata acttatgcaa gatttttttt attaatgaga tgatgtgttt gtgactgaga 1320
ttgagtcata catttcacta agaaatggtt ccaagtacca aactatcatg acccagttgc 1380
aaacatgacg ttcgggagtg gtcactttga tagttcaatt tcatcttggc ttcttattcc 1440
ttttataatt ctaattcttc ttgtgtaaac tatttcatgt attatttttc tttaaaattt 1500
acatgtcatt tattttgcct cactaactca attttgcata taacaatgat aagtgatatt 1560
ttgactcaca aaatttacat caaatttcga catcgtttat tatgttcatt ggatgattaa 1620
caaatataac aaactttgca actaattaac caccaactga atataattaa ctataactgt 1680
gaaagtagtt aaccatattt tttagatgta tatatcatcc gttgaatgta attattcata 1740
tatttgaact aagttaccct acaacttaaa gaacttaaag aactcggttt gagacctggg 1800
gacgaaaatg taatgagact ttaatgttga ctttgacacc gcaccacatg tgccttttac 1860
atatagttta tatgacaagt aatgacaatc cttgctctat tataaggcga cccttagctc 1920
caaccaaagg acgatggagt taagaaagaa actcttgctt acttgtaagg tccacacttc 1980
ttcactcacc tctcaatttc atcctacaaa aatgtccaaa cttctctttc tcacaatcac 2040
aaactcattc caaacacact ctcttctcca aaaatgtctt ccttctcagt acgtttcctc 2100
accccaccat ccatctctcg tcccaacaaa acatggctac tatctgctgc aactccatca 2160
gttgcacctg tttcaacacc acaagttgat gcatcaaggt tggagcctag agttgaggaa 2220
aaagatggtt ac                                                     2232
<210>13
<211>1383
<212>DNA
<213>人工序列
<220>
<223>待用作启动子用于调控外源基因表达的序列
<400>13
gatcctctcc ggtcaccgga aagtttcagt agaagaaaca aaacaccgtg actaaaatga 60
tactattatt ttatttattg tgtttttctt ttttctaccg gaacttttta gaacggatcc 120
caactcgttc cggggccgct acaactgaaa caaaagaaga tattttctct ctcttcagaa 180
atgtaagttt tcctttacag atacccattc accatttgat tcagatgtgg tgactagaga 240
taaagcatac taatttgact cttggaaacc cataaagttt atgttatccg tgttctggac 300
caatccactt gggggcataa cctgtgtcta tgtgtggttt ggtttccatt ctgatttatg 360
cggcgacttg taatttaaaa tctaggaggg gcagacattg aacaatccca atattttaat 420
aacttatgca agattttttt tattaatgag atgatgtgtt tgtgactgag attgagtcat 480
acatttcact aagaaatggt tccaagtacc aaactatcat gacccagttg caaacatgac 540
gttcgggagt ggtcactttg atagttcaat ttcatcttgg cttcttattc cttttataat 600
tctaattctt cttgtgtaaa ctatttcatg tattattttt ctttaaaatt tacatgtcat 660
ttattttgcc tcactaactc aattttgcat ataacaatga taagtgatat tttgactcac 720
aaaatttaca tcaaatttcg acatcgttta ttatgttcat tggatgatta acaaatataa 780
caaactttgc aactaattaa ccaccaactg aatataatta actataactg tgaaagtagt 840
taaccatatt ttttagatgt atatatcatc cgttgaatgt aattattcat atatttgaac 900
taagttaccc tacaacttaa agaacttaaa gaactcggtt tgagacctgg ggacgaaaat 960
gtaatgagac tttaatgttg actttgacac cgcaccacat gtgcctttta catatagttt 1020
atatgacaag taatgacaat ccttgctcta ttataaggcg acccttagct ccaaccaaag 1080
gacgatggag ttaagaaaga aactcttgct tacttgtaag gtccacactt cttcactcac 1140
ctctcaattt catcctacaa aaatgtccaa acttctcttt ctcacaatca caaactcatt 1200
ccaaacacac tctcttctcc aaaaatgtct tccttctcag tacgtttcct caccccacca 1260
tccatctctc gtcccaacaa aacatggcta ctatctgctg caactccatc agttgcacct 1320
gtttcaacac cacaagttga tgcatcaagg ttggagccta gagttgagga aaaagatggt 1380
tac                                                               1383
<210>14
<211>3472
<212>DNA
<213>人工序列
<220>
<223>待用作终止子用于调控外源基因表达的序列
<400>14
caagttgatg catcaaggtt ggagcctaga gttgaggaaa aagatggtta ctgggttttg 60
aaggaagagt atagaggagg tattaatcct caggagaaag ttaagattca gaaagaacct 120
atgaagcttt ttatggaagg tgggattaat gatttggcta atatgtctct tgaagagatt 180
gaaagctcta agcttactaa agatgatatt gatgttagac ttaaatggct tggtcttttt 240
catagaagga aacatcattg taagtttttt tactttcttt ttatacttca aagttctctc 300
atactctgta tttgtttatt agtttttgta gacttaaata ttctctttga tttacatagt 360
gaaactccat tcttgtttcc gaaattgtag tgtgtatagt ctagaaaatt aagaagtaga 420
caaaatgatt tatgagattg taaattgtag gctttttatc aatttattaa ttttagagac 480
caaaatttgc ctatcttatt tggaccaatt tattgtatgt taggatcgac atgagtttag 540
caaaatcatg acggcaccat gactgtgttg aagcttcttt gtgtaacttt aaccaaaatt 600
atatggcaca ccatgattat gcaaactcac cgtcaatcca aacatagaaa ttcagtgtta 660
atctttgtga caataaaaaa ctatgagtta tgttgtacta atttatttcc attgtgaaac 720
tcagatggta gatttatgat gagactaaaa ctcccaaatg gggtaacaac aagtgctcaa 780
acaagatact tggcgagtgt gataaaaaaa tatggcaaag acggatgtgc tgatgtgaca 840
acgaggcaga attggcaaat tcgaggtgta acgttacctg atgtccctga aattcttaag 900
ggccttgcag aggtcggctt gacaagtctg cagagtggaa tggacaatgt tcgaaaccca 960
gttggtaacc ctcttgctgg tattgaccct gatgagattg ttgatacaag accttacacc 1020
aatttgctgt cccaattcat cactgctaat tcacttggta atccaaccat tacaaacttg 1080
taagtctaaa ctatctcatc tttatatttc actcattata tcatattagt agttagttac 1140
ttgcattgca agcattacgt gaccgtgtgt agcctctaaa tccttttgat aatatgtgca 1200
ggccaaggaa gtggaatgta tgtgtgatag gttcccatga tcttttcgag catccgcata 1260
ttaacgatct tgcttatatg cctgctaata aggatggtcg atttggattc aacttattgg 1320
tgggtggttt ctttagtccc aagcgatgtg ctgaagcagt tccacttgat gcatgggtct 1380
ctgcagatga tgttatccca ctttgtaaag ctgtccttga gacctatagg gacctcggca 1440
caagagggaa tagacagaaa accagaatga tgtggttgat cgatgaactt gtaagttacc 1500
actttttttc ttcacatatt attaactgaa gtgactttaa cgaccatttt acaattgaaa 1560
tttaagtgga ttttagccct atcattacaa gaacaaattt gttaattcac tagcaagagc 1620
aattccactt tggcttggac atgacaagtg tttgtgaaat gcaggggata gaagtattca 1680
gatcagaggt ggaaaaaaga atgccagaga agaagctaga gagagcatcc aaagaagaac 1740
ttgtccaaaa acaatggaaa gaggagacat cttaggtgtt catccacaaa aacaagaagg 1800
tttaagctat gttggaattc acattccagt tggtagaatc caagcagatg agatggaaga 1860
gctagctcgt atcgccgatg aatacggaac cggagaacta aggctaaccg tggagcaaaa 1920
cataataatt ccaaatgtgg aaaactcaaa acttgatgca ttgctaaatg aacctctctt 1980
gaaagacaaa ttctcaccag aaccttccat cctaatgaaa acacttgtgg catgcactgg 2040
taaccaattt tgtggccaag caataattga aacaaaacaa agagctttaa aagtaactga 2100
agaagttgaa agacatgtgg ctgtgagcaa accagtgaga atgcattgga ctggttgtcc 2160
taacacttgt ggtcaagttc aggttgctga tattggtttt atgggttgta tggctaggga 2220
tgagaatggt aaggctactg aaggtgttga tattttcctt ggtgggagaa ttggaagtga 2280
ttctcattta gctgaggtgt ataagaaagg tgtcccttgc aaggacttgg tgcctattgt 2340
agctgatatt ttggttaaat attttggagc tgtccaaagg aatagagaag aaggggatga 2400
ttaaagtata taggtatttg gtgattttaa ttgcctctac acaaaattat tatgttctgt 2460
ccaaaatata aagtcacaag ggataattga gattgagatg cagcacgcca cacatgaact 2520
tgtacatttg gataagtcat ttttcattgc tattttataa gttacacttt gaattttata 2580
ataaatttta ttttatttca aggaccagat tttataagga aaccgctaat ctaactatct 2640
ttactcgtaa tttgtcattt gagagctacg gagatcgttg agtttacgta tgagtgttta 2700
gtctcacatt aattatgaat ggtcaaaatg ttaaatttat aagagatgta atctatatac 2760
ctaatgcatt aaaaatttgg atggagatgc gacgcccccc ttttttgtgg tcctgaagta 2820
tagacttgtt gtcgcttctg gtgcactctc atacttccca acaaggagaa aaaactacca 2880
taacaattaa caaactaaca tttgttattt aaaaaaacat acggatactg ttttttcccc 2940
atttattagg aagatgatgg cttggatttc aatggctgag tttatttttt ttttggtcgg 3000
gagttgaagt atcgggaaaa ctaaatatgc tatgacttta aacattgtgt tgatatatga 3060
ttagttttca acttacttaa aaagtggcaa actagtttag tggttctctc ccttccttgt 3120
agttcaagga acatgggttt gaactctgtc caaatttttg tactttcaat tatccataca 3180
tttaaaagct atataccaca tcattatatt caagtcaatg atcatgcggc ctgccacatt 3240
agcatcgatg tacacattaa ttttaagtgg catgaacaca ttaacatttc ataaaagcta 3300
tgtgccagat catcattcaa gtctatgcac acatggtcaa cacattagta ccattttttt 3360
ttttattgtt gatcagattg gatgtcggta ttgttgtgat gctacaaact caaacaatct 3420
ccagctgtta gagaacgtcg aaaatgaatg catcacgggt gcacacttag at         3472
<210>15
<211>617
<212>DNA
<213>人工序列
<220>
<223>待用作终止子用于调控外源基因表达的序列
<400>15
agtatatagg tatttggtga ttttaattgc ctctacacaa aattattatg ttctgtccaa 60
aatataaagt cacaagggat aattgagatt gagatgcagc acgccacaca tgaacttgta 120
catttggata agtcattttt cattgctatt ttataagtta cactttgaat tttataataa 180
attttatttt atttcaagga ccagatttta taaggaaacc gctaatctaa ctatctttac 240
tcgtaatttg tcatttgaga gctacggaga tcgttgagtt tacgtatgag tgtttagtct 300
cacattaatt atgaatggtc aaaatgttaa atttataaga gatgtaatct atatacctaa 360
tgcattaaaa atttggatgg agatgcgacg cccccctttt ttgtggtcct gaagtataga 420
cttgttgtcg cttctggtgc actctcatac ttcccaacaa ggagaaaaaa ctaccataac 480
aattaacaaa ctaacatttg ttatttaaaa aaacatacgg atactgtttt ttccccattt 540
attaggaaga tgatggcttg gatttcaatg gctgagttta tttttttttt ggtcgggagt 600
tgaagtatcg ggaaaac                                                617
<210>16
<211>502
<212>DNA
<213>人工序列
<220>
<223>待用作终止子用于调控外源基因表达的序列
<400>16
ttgtacattt ggataagtca tttttcattg ctattttata agttacactt tgaattttat 60
aataaatttt attttatttc aaggaccaga ttttataagg aaaccgctaa tctaactatc 120
tttactcgta atttgtcatt tgagagctac ggagatcgtt gagtttacgt atgagtgttt 180
agtctcacat taattatgaa tggtcaaaat gttaaattta taagagatgt aatctatata 240
cctaatgcat taaaaatttg gatggagatg cgacgccccc cttttttgtg gtcctgaagt 300
atagacttgt tgtcgcttct ggtgcactct catacttccc aacaaggaga aaaaactacc 360
ataacaatta acaaactaac atttgttatt taaaaaaaca tacggatact gttttttccc 420
catttattag gaagatgatg gcttggattt caatggctga gtttattttt tttttggtcg 480
ggagttgaag tatcgggaaa ac                                          502
<210>17
<211>25
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>17
gatattgatg ttagactcaa gtggc                                       25
<210>18
<211>21
<212>DNA
<213>人工序列
<223>待用作引物的序列
<400>18
cacysattcc acttcctwgg c             21
<210>19
<211>27
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>19
ttgtcacatc agcacatccg tctttgc        27
<210>20
<211>27
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>20
tcgccaagta tcttgtttga gcacttg        27
<210>21
<211>27
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>21
agagcccggg agaagagagt gtgtttg        27
<210>22
<211>28
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>22
ttctcccggg ggacgagaga tggatggt       28
<210>23
<211>30
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>23
ttctcccggg gttgaaacag gtgcaactga    30
<210>24
<211>28
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>24
ttctcccggg taaccatctt tttcctca      28
<210>25
<211>24
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>25
cacacttctt cactcacctc tcaa          24
<210>26
<211>21
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>26
atctaggagg ggcagacatt g             21
<210>27
<211>24
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>27
tcggtataaa gacttcgcgc tgat            24
<210>28
<211>27
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>28
atgtcttcct tctcagtacg tttcctc         27
<210>29
<211>30
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>29
caagttgatg catcaaggtg ggagcctaga      30
<210>30
<211>30
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>30
agaagagctc agtatatagg tatttggtga      30
<210>31
<211>30
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>31
agaagagctc ttgtacattt ggataagtca      30
<210>32
<211>30
<212>DNA
<213>人工序列
<220>
<223>待用作引物的序列
<400>32
agaagaattc gttttcccgatacttcaact    30

Claims (2)

1.一种调控外源基因在转基因植物的叶子中转录的分离的启动子，所述分离的启动子是SEQ ID NOS：1-13所示的核酸序列。
2.权利要求1的分离的启动子，其中所述植物是苜蓿。
CNB008138680A 1999-10-04 2000-10-02 调控外源基因转录的方法 Expired - Fee Related CN100427603C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US15713399P 1999-10-04 1999-10-04
US60/157,133 1999-10-04

Publications (2)

Publication Number Publication Date
CN1377419A CN1377419A (zh) 2002-10-30
CN100427603C true CN100427603C (zh) 2008-10-22

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