数学课件-Chapter-7.ppt

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1、1/71Chapter 7 /第第7章章Regulation of Gene Expression in eukaryotes7.1 Histones and Transcriptional Regulation7.2 Post-Transcriptional Regulation7.3 Nuclear Export7.4 RNA stability7.5 Translational control 7.6 mRNA localization7.7 Protein regulation7.8 Experiments真核生物基因表达调控真核生物基因表达调控7.1 组蛋白与转录调控组蛋白与转录调控

2、7.2 转录后调控转录后调控7.3 细胞核输出细胞核输出7.4 RNA稳定性稳定性7.5 翻译调控翻译调控7.6 mRNA定位定位7.7 蛋白质调控蛋白质调控7.8 实验研究实验研究2/71Same DNA,different cells相同的相同的DNA、不同的细胞、不同的细胞Neural cells神经细胞神经细胞Blood cells血液细胞血液细胞A muscle cell肌肉细胞肌肉细胞Human cells 人体细胞人体细胞3/71We are going to learn 4/717.1 Histones and Transcriptional RegulationHomeodo

3、main 同源异型域同源异型域Leucine zipper 亮氨酸拉链亮氨酸拉链Zinc finger 锌指锌指HLH 螺旋螺旋-环环-螺旋螺旋5/71Histones /组蛋白组蛋白?Chapter 26/717.1.1 Histones and DNA organization组蛋白与组蛋白与DNA组织组织核心组蛋白核心组蛋白八聚体八聚体7/71Histones contain many amino acids with positive charges组蛋白含有许多带正电荷的氨基酸组蛋白含有许多带正电荷的氨基酸His/Lys/Arg+8/71Nucleosome /核小体核小体9/71T

4、he Beads-on-a-string model线线 珠珠 模模 型型 60 bp 150 bp10/71The 30nm fibre /30nm纤维纤维11/71Levels of DNA organizationDNA组织的水平组织的水平12/71Now showingChromosome PackingFile:biophoto7 Lehninger Principles of Biochemistry Three dimensional packing of nuclear chromosome(5)13/71Euchromatin and heterochromatin常常染色质

5、染色质 和和 异染色质异染色质14/717.1.2 Histones and Transcription组蛋白与转录组蛋白与转录15/71Structure of histones /组蛋白的结构组蛋白的结构Histone tail16/717.1.3 Covalent modification of histones组蛋白的共价修饰组蛋白的共价修饰17/71Acetylation /乙酰化作用乙酰化作用18/71CH3 CH3CH3Histone code /组蛋白密码组蛋白密码K9K4K9K4RepressionK9K4CH3Activation19/71Histone code /组蛋白

6、密码组蛋白密码K14K8PH10K8PH10AcK14PH10AcK14K8EffectEffectEffect20/71Histone code /组蛋白密码组蛋白密码PH10AcK14K8EffectA coded lock（密码锁）（密码锁）21/717.1.4 Proteins that recognize and modify histones识别和修饰组蛋白的蛋白质识别和修饰组蛋白的蛋白质Chromatinremodelingprotein22/71Swi/Snf complex23/71Specific transcription factors attract various

7、enzymes特异转录因子吸引不同的酶特异转录因子吸引不同的酶Reference:KarpusasM,NolteM,BentonCB,MeierW,LipscombWN,GoelzSThecrystalstructureofhumaninterferonbetaat2.2-AresolutionProc.Natl.Acad.Sci.U.S.A.v94,p.11813-11818Description:HumanInterferon-BetaCrystalStructure.Deposition:1997/9/9Author:KarpusasM,NolteM,LipscombWTaxonomy:

8、HomosapiensMMDB:8039PDB:1AU1StructureNeighbors:VASTINF-24/71Regulation of INF-gene(1/3)INF-gene25/71Regulation of INF-gene(2/3)“There is not enough room for me.Please help to push away the histones.”26/71Regulation of INF-gene(3/3)“Thank you.I got it”27/717.2 Post-Transcriptional Regulation转录后调控转录后调

9、控Chapter 528/71Sex determination of fruit flies果蝇的性别决定果蝇的性别决定29/71Alternative splicing of the Sxl gene 30/71Alternative splicing of the Sxl gene 31/71Further studying R.F.Weaver,Molecular Biology,Chapter 1432/71Alternative polyadenylation /可变聚腺苷化可变聚腺苷化33/717.3 Nuclear Export /细胞核输出细胞核输出34/71Export o

10、f heat shock protein mRNAs热休克蛋白热休克蛋白mRNA的输出的输出Yeast cellswww.zeiss.de/C12567BE0045ACF1/ContentsWWWInte35/71HIV:human immunodeficeincy virusHIV36/71Export of HIV mRNAs/HIV mRNA的输出的输出37/717.4 RNA stability /RNA稳稳定性定性38/71Common mechanism for mRNA degradation39/717.4.1 mRNA Stability Regulationby Prote

11、ins蛋白质调控蛋白质调控mRNA稳定性稳定性ARE:AU-rich elementUTR:untranslated region40/71Function of Protein TTPGrowth signalTTP:a CCCH zinc finger protein 41/71Transferrin /运铁蛋白运铁蛋白www.umassd.edu/cas/chemistry/guo/guoresearch.html Membranecoated vesicleFe3+Fe3+EndosomepH 5.0Fe3+Fe3+pH triggersFe3+releaseTransferrin c

12、ycleFe3+Fe3+pH 7.4TransferrinreceptorsDiferrictransferrinCytosol42/71Regulation of transferrin by aconitase顺乌头酸酶对运铁蛋白的调控顺乌头酸酶对运铁蛋白的调控43/717.4.2 mRNA Stability Regulationby Small RNAs小小RNA调控调控mRNA稳定性稳定性RNAstabilityRegulatedby proteinsRegulated by small RNAsmiRNAsiRNA44/71RNA interference(RNAi,RNA干涉干涉

13、)RNA interference:A process that uses siRNA or miRNA to induce degradation of a target mRNA.（一种（一种siRNA或或miRNA诱导目标诱导目标mRNA降解的过程）降解的过程）www.english.vietnamnet.vn/./2006/10/618962/Two U.S.scientists won Nobel Prize in medicine(October 4,2006)U.S.scientists Andrew Fire and Craig Mello won the Nobel Priz

14、e in physiologyor medicine Monday for discovering a powerful way to turn off the effect of specific genes,opening potential new paths for disease treatment.45/71Functions of siRNA and miRNA(1/3)46/71Functions of siRNA and miRNA(2/3)47/71Functions of siRNA and miRNA(3/3)48/71RISC:RNAi Silencing Compl

15、exRNAi沉默复合体沉默复合体 1U04.val49/71Origin and function of miRNA50/71Origin and function of siRNA51/717.5 Translational control /翻译调控翻译调控Translational control may be divided into two broad categories,global control and mRNA-specific control.The latter is used to control the translation of individual mRNAs

16、.By contrast,global control is used to regulate the translation of all mRNAs in the cell indiscriminately.翻译调控可以被分翻译调控可以被分成两大范畴：成两大范畴：全局全局控制控制和和mRNA特异特异性控制性控制。后者用来。后者用来控制单个控制单个mRNA的的翻译。相反，全局翻译。相反，全局控制是对细胞中所控制是对细胞中所有有mRNA实施不加实施不加区别的调控。区别的调控。52/717.5.1 Global Control/全局控制全局控制www.uniklinikum-giessen.de

17、/./res_ires.htm Picornavirus小核糖核酸病毒小核糖核酸病毒Chapter 653/71Global control through phosphorylation54/71Normal cycle at translation initiation55/71Global control through 4E-BP56/71Global control through 4E-BP57/717.5.2 mRNA-Specific ControlmRNA特异性控制特异性控制Mechanisms of translation regulation also exists at

18、 target specific mRNAs or groups of mRNAs,rather than all transcripts.This is known as mRNA-specific control,and it depends very much on sequences within individual mRNA transcripts.翻译调控机理也存在翻译调控机理也存在于对特殊的目标于对特殊的目标mRNA分子或目标分子或目标mRNA群的调控，而群的调控，而不仅仅用于调控所有不仅仅用于调控所有的转录产物。这就是的转录产物。这就是mRNA特异性控制，特异性控制，它在很大

19、程度上依赖它在很大程度上依赖于于单个单个mRNA转录产转录产物内部的序列物内部的序列。58/71mRNA with CPECPE:Cytoplasmic Polyadenylation Element （细胞质聚腺苷酸化元件细胞质聚腺苷酸化元件） 59/71CPEB,Maskin and eIF4E60/71Ferritin /铁蛋白铁蛋白Crystal Structure Of Ferritin(Tm1128)From Thermotoga MaritimaFile:Ferritin 1VLG.valFe61/71Regulation of ferritin by aconitase顺乌头酸

20、酶对铁蛋白的调控顺乌头酸酶对铁蛋白的调控62/717.6 mRNA localization /mRNA定位定位Regulatory mechanisms also exist to control where proteins are made.Cells are not uniform mixtures of molecules.Some proteins are needed in certain parts of the cell,and some must be absent from certain parts.This is especially true for morphol

21、ogically complex cells like neurons.调控机理还能用来决调控机理还能用来决定在哪儿生产蛋白质。定在哪儿生产蛋白质。细胞并不是均匀的分细胞并不是均匀的分子混合物。某些蛋白子混合物。某些蛋白质需要在细胞的某些质需要在细胞的某些部位出现，而有些则部位出现，而有些则一定不能出现在那里。一定不能出现在那里。在像在像神经元神经元这样的形这样的形态极为复杂的细胞中态极为复杂的细胞中这种情况更为明显。这种情况更为明显。63/71Many proteins have no signalsMany proteins contain signals that cause them

22、to localize to specific areas after translation.However,many other proteins do not contain such signals.Their localization depends to a great extent on where in the cell their mRNA is translated.许多蛋白质都带有信许多蛋白质都带有信号，使它们在翻译后号，使它们在翻译后被定位到特定的区域被定位到特定的区域中去。然而，还有许中去。然而，还有许多蛋白质并不含有这多蛋白质并不含有这样的信号。它们的定样的信号。它

23、们的定位在很大程度上依赖位在很大程度上依赖于它们的于它们的mRNA在哪在哪儿进行翻译儿进行翻译。64/71Three mechanisms for mRNA localizationmRNA定位的三种机理定位的三种机理65/71Localization of-actin mRNA-肌动蛋白肌动蛋白mRNA的定位的定位A fibroblast cell66/71Localization of-actin mRNA-肌动蛋白肌动蛋白mRNA的定位的定位67/717.7 Protein regulation /蛋白质调控蛋白质调控68/717.8 Experiments /实验研究实验研究7.8.1

24、 Beads-on-a-string Structure 线珠结构线珠结构7.8.2 Repression of Gene Expression in Heterochromatin 异染色质中基因表达的阻遏异染色质中基因表达的阻遏69/717.8.1 Beads-on-a-string Structure线珠结构线珠结构A pearlbracelet珍珠手链珍珠手链70/71DNase treatment71/717.8.2 Repression of Gene Expression in Heterochromatin异染色质中基因表达的阻遏异染色质中基因表达的阻遏Yeast colonies are whiteYeast colonies are red.