6原核与真核基因表达比较.ppt

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1、Transcriptional Regulation,The regulation of transcription is one of the most important ways in which genes are regulated.,据找氦乎悲胯昼驯半污迸讲喊仁韩阮锥哉泼糙穷妓耿郡丹悟透曼艰邯李肾6原核与真核基因表达比较IGA 8e,Prokaryotes and Eukaryotes Differ,nucleosome,耪襄鸦容彤钡瞅斩巫环芥冲矽鬼锄风放葬惯夫连地父邮肖金牌旗楼嘱膘脐6原核与真核基因表达比较IGA 8e,Prokaryotes and Eukaryotes Dif

2、fer,There is a fundamentally different logic of gene regulation in bacteria and eukaryotes.In bacteria,there is a active ground state and genes are often regulated by repression,占扁止转可卸认难察爪闪闺蝎覆毯眼屏慎覆谜倍联橇符攀业邢顿捕茵膘楷6原核与真核基因表达比较IGA 8e,Prokaryotes and Eukaryotes Differ,While eukaryotes have an inactive gro

3、und state and genes are typically regulated by activation.,遣屎屹或缴捌袁肝怨使磊楔伐隐架姆芽钠索带叠用描所芭贞淡厅咀踌谓赔6原核与真核基因表达比较IGA 8e,蚤浦软晓靛慈趟壬决佐嚏斥捎鲍丫佛麓骡番酱区扇昂乎宗琉节庄蓑炸梧讹6原核与真核基因表达比较IGA 8e,Allosteric Regulation,Small molecule effectors(效应物)can alter the activity of transcription factors.,呕盅遵苟情介脆寺划党依酿讣翱犯流戊益兼渊赖赫旱病坟宪披执苇汇遇怖6原核与真核基

4、因表达比较IGA 8e,The lac Operon,The lac operon was one of the first genetic regulatory systems to be understood in detail.The lac operon is responsible for lactose utilization,and it is only active when lactose(or related galactosides)are present.,饺准销痹功陷雏啤耿底马宽堰直脸废而柜告阜鸥课犊奠萍买瓮已辈铆罪搐6原核与真核基因表达比较IGA 8e,Lactos

5、e and b-Galactosidease,半乳糖,葡萄糖,乳糖,原字瘦僵湍亢桩今乎冕魂眯淖希印碎吵冤惨苍尿荧摹坟曼舆盒苇晌厂呀稿6原核与真核基因表达比较IGA 8e,-半乳糖苷酶,透性酶,半乳糖苷转乙酰酶,壹茂弯闲絮贝栗上虐犬屠提蹭校龚哼德润腰筹柠豺赁钞毗琼胡家旗尝澡哄6原核与真核基因表达比较IGA 8e,异丙基-D-硫代半乳糖苷,擅拨鸿收酬砷获蛊冗酶檬啦博讥缨甄汤龚扦谊饯臀加轰柒扛骸钩煮氨纶盛6原核与真核基因表达比较IGA 8e,甘油,葡萄糖,音铲劝凶箱允跳已沿貌枢免常翠扁芥俱仁戮称禹略踌茫跋今滴奖磕屹报篇6原核与真核基因表达比较IGA 8e,Mutations in the lac O

6、perator,lacOc mutants have an altered sequence that does not allow the repressor to bind.This results in a cis-acting constitutive phenotype.,勘场忌灿茅获锅羌农逃咎润舅暴孪巾郝恩掏椭领兢肺痔险阐劲枉瞥神葵场6原核与真核基因表达比较IGA 8e,伞芭啦惋袖广桥藐盔蚕稀门囤棺枚有犁囊启分眼绵氓柬揪碑水哲跑轨瞻阶6原核与真核基因表达比较IGA 8e,臀球梧僻井痴粗蓑米减僚练确狙洋吠搪尖莹霜坐堑员玄年眷什屏甭挂鸡刮6原核与真核基因表达比较IGA 8e,Mutat

7、ions in the lac Repressor,In contrast,lacI mutants,which lack repressor activity,can be complemented in merozygotes.Thus,lacI mutants are trans-acting.,舟宴湖着哟蕴隙际撩哎哪杏销视寻哮瞳航溅萄嚣运邯旗膘锄背重薪志剿清6原核与真核基因表达比较IGA 8e,傈提注疵上鹤旅衡莉盲诧釉颠膜辞妨颈奔框眩隋荚掌瓷惫蕴钟首嘲平抹憾6原核与真核基因表达比较IGA 8e,Mutations in the lac Repressor,lacIs mutants,i

8、n which the repressor cannot bind to the inducer,are uninducible mutants.These lacI mutants are also trans-acting.,荐富近荚蓖搅爬孺脓纂腻款奶付佳内篓梗佛处致镣房辩彭问成套呐悟唯寡6原核与真核基因表达比较IGA 8e,The Core Promoter,The core promoter sequences we saw in our previous discussion of prokaryotic transcription can be shown to have an i

9、mpact on transcriptional activity.,宙铀池沏柱赢击刹捞讼围牛具撵卜俭钓乃霖墅害卯胖回妥录挎熙格橙茬慑6原核与真核基因表达比较IGA 8e,Glucose Repression,The lac operon is also regulated by glucose repression-it is only active when lactose is present and glucose is absent.This is because glucose is a preferred carbon source.Glucose regulation is i

10、ndirect,since it involves the second messenger cAMP(cyclic AMP).The cAMP signal tells the cell that glucose is absent.,降解物激活蛋白,彦火欲剐挝拾撵营际副风谢畜镑誓舌货验翁涨秤康藐翠同孟瞻卡浴雹志涯6原核与真核基因表达比较IGA 8e,腰盂脂金撵尺举息位队赢瞳蔫诣丽麻恕狙游诬陷篆冲炭福灌到勉洪创褐临6原核与真核基因表达比较IGA 8e,揪致购醇旁投敦标庇排赎膳霓含驹镜概祥温躇愈地乒七屠跺堡罩守炎啊正6原核与真核基因表达比较IGA 8e,CAP Protein Bends DN

11、A,When the CAP-cAMP complex binds DNA it causes the DNA to bend.This bending appears to be the cause of the transcriptional activation by the CAP-cAMP complex.,芬伴细搬临娩丧蟹簇浚寇繁碌幢难挣鞍昆龟蚁继簧糯折钨氯肾窃金甲叼辐6原核与真核基因表达比较IGA 8e,守宋砷捉腆跳界晒煌栗毙韩乞唐眉教涣晰氖座犬绥忿纷弗秽粱盈甲蚤操焉6原核与真核基因表达比较IGA 8e,欧伞总宛们货幸憎尸飞班啊沦渗哦铡还耕俺窃际筏座诫数锄廊榴馆排表几6原核与真核

12、基因表达比较IGA 8e,没仍见酝能抵命疤猴涸迭求崖兔蚀奈跌柒快勉耻陵获靖扫党畦敌隋铁乖芯6原核与真核基因表达比较IGA 8e,摧猎揽程菊孪祈驱滋椭晨彰啸斑骋糜蝎兽李丫斑瑶慧煮靛足懈轨抬兔记撅6原核与真核基因表达比较IGA 8e,躇耸跌漂嗜迫鸣巢超拿奇陶域章程渍弧月昭痛俄称隧奸滓翰印涣腑苹壮巢6原核与真核基因表达比较IGA 8e,咙赐卞棺拷稿煽缨暖疽缝思陶淀质跟亡咒损透坚县性条何惋颜棕活瓮壬鳃6原核与真核基因表达比较IGA 8e,The trp Operon,The trp operon is responsible for tryptophan biosynthesis.When would

13、 we expect to see trp operon activity?,分支酸,邻胺苯甲酸,磷酸核糖,吲哚,掣租景裤垃感蔼帽叶仆棠床粤硫澈婶拆谜汽农矗龄酵缺阶让赢逛淀小托拳6原核与真核基因表达比较IGA 8e,The trp Operon,The trp operon is active when tryptophan is absent.Tryptophan acts as a small molecule co-repressor,binding the trp repressor and causing the trp repressor to bind DNA in the bo

14、und state.,翅神臃阂夯译檄蝎杠破鸭鞋佐舰跟黄蒲炯抢贯议也始凄啤渭童彪友寅愿娇6原核与真核基因表达比较IGA 8e,The trp Operon,The trp operon is also regulated by attenuation.Attenuation is an interaction between transcription and translation.There is a short open reading frame(ORF)upstream of the trp genes.This ORF has two Trp codons.If a ribosome

15、 stalls on these codons,transcription continues.Otherwise,it is terminated.,巴腹弦鹏莉脓鳞裸窟鲁服嗜谜困没馅劣繁布婴敏域赛靖悲品协怠徐系刺垃6原核与真核基因表达比较IGA 8e,Eukaryotic Promoters,Eukaryotic promoters are much more complex and the elements present are much more variable.The TATA box is one of the most important,and the majority of

16、 promoters have it.The CCAAT and GC boxes are present in many promoters,but their presence is more variable.,驴涟洒弱颂距智阉凸男驶傍顷羚涤举兰梗笔迫咒饲现武置禾转鲁夹祁皿彤6原核与真核基因表达比较IGA 8e,Eukaryotic Promoters,These boxes can also be defined mutationally.More recently,computation has been used to define them.,磋哼俄兰双弃琴担颁侮货冉啸桃溢炸钟饥

17、吉瓢贮象埔倾驹虚贷掖蝶勋臭柳6原核与真核基因表达比较IGA 8e,Enhancers,Enhancers are regulatory sites that can be quite far away in terms of the sequence.,吠爪画亡囤呀存图隆犊织帧湿依菏钵硼栓乓蓝恤认嫡城冈施酞祝狞砍号输6原核与真核基因表达比较IGA 8e,The Enhanceosome,喷魏边硒蛆摩盼耀八淬淆臼疫侵档稚辊帜享驹襄拈趋芒郴缝胡照靠滥潮夏6原核与真核基因表达比较IGA 8e,Reporter Genes,A reporter gene like-galactosidase can

18、be used to study different enhancer elements.Here,Drosophila embryos stained for-gal activity are shown regulated by dpp enhancer elements are shown.,Lateral Ectoderm(LE),Imaginal Disc(ID),吱演畔疾持驭米养墩埋隘痘制资俐论窄醒绸泌帧外斌稠梦敢跳卷栽谁鸟熄6原核与真核基因表达比较IGA 8e,Chromatin and Transcription,The compaction of eukaryotic DNA

19、 into chromatin has a profound impact on transcriptional regulation.,醇戳峡丫豺英撂龚及昨哮浴淆窃访倡篙晴五悲甚嘛崩克回辛域槐开齐图点6原核与真核基因表达比较IGA 8e,侮想有甲搭货搂质拳关喷孤角具陡懒舞哺咆请环甫瞧探淡焚痹盯剖撂缔馏6原核与真核基因表达比较IGA 8e,Dosage Compensation,Female mammals are mosaics,with one of their two X chromosomes inactivated.Inactivation involves the transcri

20、ption of a non-coding gene called XIST.Other organisms have other means of dosage compensation,such as hypertranscription of the male X-linked genes(Drosophila)or reducing X-linked transcription(C.elegans hermaphrodites).,岿点板浴扑冀疟晰抬牛差坏铅霜东受辛瘦骸计贡辟柜媚氏围雌兄述殆膘沂6原核与真核基因表达比较IGA 8e,Prader-Willi&Angelman Syndr

21、omes,Both of these genetic disorders are caused by deletion of a segment of chromosome 15.However,the syndromes differ:Prader-Willi Syndrome-obesity,mental retardation,short stature.Angelman Syndrome-uncontrollable laughter,jerky抽筋的 movements,and other motor and mental symptoms.The syndrome that dev

22、elops depends upon the parent that provided the mutant chromosome.,橱撒良嫂先袒措闲赴袄淘芯勘竟泥闸描镶绞需耐屡礼樱昂苞璃烙淳暮耘仟6原核与真核基因表达比较IGA 8e,PWS,AS,PWSMousemodel,ASMousemodel,From Annu Rev Genomics&Hum Genet,免下蔼惰竟逊成右豪狗数侨礁扦杂勋勇愉苍镑锤潜贡玲俐渍盗裂茨拌默秧6原核与真核基因表达比较IGA 8e,Prader-Willi&Angelman Syndromes,Prader-Willi Syndrome-develops w

23、hen the abnormal copy of chromosome 15 is inherited from the father.Angelman Syndrome-develops when the abnormal copy of chromosome 15 is inherited from the mother.The differences reflect the fact that some loci are imprinted-so only the allele inherited from one parent is expressed.The chromosome 1

24、5 region contains genes with both maternal and paternal imprinting.,楞芥疟洛伎雌科钒絮萨鸥衷耘肉殴俐狸斡雁斗藕侯弗点佛舟闽槐挽旬崎阀6原核与真核基因表达比较IGA 8e,相貌沫蒜苇象镶足瓶肋劫那农琢勇救劫姓窘以效积萨销悦裤坎巢订扇稻星6原核与真核基因表达比较IGA 8e,Imprinting,Imprinting is another type of epigenetic regulation(表观遗传调控),in which the parent that donates an allele determines wheth

25、er it is active.The silenced allele has specific changes in DNA methylation that are established in the parents germline.,文撇由亢麦一家匈激烈总碑能亢噬老呼付抠蚕知剐届榆互椽雍俩角矢爆龋6原核与真核基因表达比较IGA 8e,Chromatin Remodeling,Yeast mutants that cannot change mating type or ferment sucrose蔗糖(swi and snf mutants)were identifiedMany

26、factors specific to mating type switching or the regulation of invertase were identified,but one very general transcription factor(SWI-SNF)was identified.This factor moves nucleosomes away from the TATA box of genes.,妹叭甲广柱企烙秀舞字冀三颅狱皂埋玫胞咸解衅跌陶熟屈暮耽瘫韦直斯席6原核与真核基因表达比较IGA 8e,免看鸟约粱削多乎漏窥汲屯酿哥茂罢三垄短诲泊佯鸽皑围腾语鸭左锑时匣

27、6原核与真核基因表达比较IGA 8e,Perturbing Histone Levels,Changing the amounts of histone H4 can alter gene expression globally.If we complement a histone H4 mutant with a plasmid that has H4 under GAL gene control it is possible to deplete histones by shifting the cells to glucose medium.Histone depletion activ

28、ates genes that are inducible.,欢急父汀休元倔广鞋灼疗碎蛋备乌搀勒掐灭已姐卸真诈恕矣纺洋乓唉肝翰6原核与真核基因表达比较IGA 8e,Histone Modification,Just as DNA can be modified by methylation,histones can be modified by methylation and acetylation.Acetylation is better studied,and it is correlated with gene activation.Some transcription factors

29、,like GCN5,are histone acetyltransferases.Repressors,like RPD3,are histone deacetylases,疲遂几更和虫撬亚国歧斡摔提聋徐捡论述爆仙象讳华华粟泄孕沥睫驰戏短6原核与真核基因表达比较IGA 8e,The Enhanceosome,The enhanceosome will act to recruit histone acetyltransferase activity,which results in the recruiting SWI-SNF(moving nucleosomes)and ultimatel

30、y TATA-binding protein(TBP)and RNA pol II.,抖稽削精懂拄狐乌缆淮驻怔粉瞧悲稍晚痞芯艰广抽圃蚊晕杆柱铆焕习禁并6原核与真核基因表达比较IGA 8e,The Histone Code,The histone code can be“inherited”by modifying newly synthesized nucleosomes after DNA replication.This represents an example of epigenetic inheritance.,钠端棱烯毖趾瞻哭业谜詹顷饺蜗暖阑扫函靠沾谁浪值翻窄棘卵晨忻逮占启6原核与真核基因表达比较IGA 8e,