数学课件-Chapter-4.ppt

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1、1/76Chapter4TranscriptioninEukaryotes:MechanismandRegulation4.1EukaryoticRNApolymerases4.2EukaryoticPromoters4.3GeneralTranscriptionFactorsandInitiation4.4SpecificTranscriptionFactorsandTranscriptionalRegulation4.5Structuresofspecifictranscriptionfactors4.6Experiments4.1真核生物真核生物RNA聚合酶聚合酶4.2真核生物启动子真核

2、生物启动子4.3通用转录因子与通用转录因子与转录起始转录起始4.4特异转录因子与特异转录因子与转录调控转录调控4.5特异转录因子的结构特异转录因子的结构4.6实验研究实验研究2/76TranscriptioninEukaryotes:MechanismandRegulation真核生物转录：机理与调控真核生物转录：机理与调控ProkaryoteEukaryote3/76Transcriptioninprokaryotes4/76TranscriptionineukaryotesEukaryoticRNApolymeraseIIandtranscriptionfactorsSpecifictra

3、nscriptionfactorGeneraltranscriptionfactorsGeneraltranscriptionfactors5/764.1EukaryoticRNApolymerases真核生物真核生物RNA聚合酶聚合酶6/76LocationsofRNApolymerasesNucleolus(RNApolymeraseI)Nucleoplasm(RNApolymeraseIIandIII)7/76RNApolymeraseIRNApolymeraseIrRNAprecursorProcessing5.8SrRNA18SrRNA28SrRNA8/76RNApolymerase

4、IIIRNApolymeraseIIIRNAprecursorProcessing5SrRNA4.5StRNAU6snRNA9/76RNApolymeraseIIRNApolymeraseIIRNAprecursorProcessingsnRNAsTranslationProteinmRNA10/76RNApolymeraseIIHoloenzyme:Coreenzyme(,&)+SubunitRNApolII:Coresubunits(1,2&3)+Subunits4-1211/76RNApolymeraseII12/764.2EukaryoticPromoters真核生物启动子真核生物启动

5、子ProkaryoticpromoterEukaryoticpromoter13/76EukaryoticPromoters真核生物启动子真核生物启动子“IwouldliketohaveTATAboxandInitiatorasmypromoter.Whatwouldyoulike?”“Well,IpreferBREandDPE.”14/76TATAboxTATAAA-10boxTATAAT15/76SpecializedgeneshaveTATAboxesTATAboxSpecializedgenes+HousekeepinggenesGenesofdevelopment16/76DPE:D

6、ownstreamPromoterElementGCGAT17/76Initiator/起始子起始子PyPyANPyPyTA18/76BRE:TFIIBRecognitionElementCGCCCGCCGGGGGGCCACCA19/764.3GeneralTranscriptionFactorsandInitiation（通用转录因子与转录起始）（通用转录因子与转录起始）ProkaryoticRNApolymerasepre-initiationcomplexEukaryoticRNApolymeraseII:“Ineedhelpfromotherproteins.”20/764.3.1TF

7、IID21/76TBP:TATA-BindingProtein22/76Show3DstructureofTBPFile:TBP-TATAboxcomplex1.val23/76TAFIIs:TBP-AssociatedFactorsII24/76TAFIIs:1)BindingtoDPEorInr25/76TAFIIs:2)BindingtoActivator26/764.3.2OtherTFIIs27/76NowshowingInitiationofTranscriptionFile:biophoto7LifeInitiationoftranscription(5)28/764.3.3Ge

8、neralTranscriptionfactorsforRNAPolymeraseIandIIIRNA聚合酶聚合酶I和和III的通用转录因子的通用转录因子29/761.GeneralTFsofRNApolymeraseI30/762.GeneralTFsofRNApolymeraseIII31/76GeneralTFsofRNApolymeraseIII32/764.4SpecificTranscriptionFactorsandTranscriptionalRegulation特异转录因子与转录调控特异转录因子与转录调控Specifictranscriptionfactor33/76Spec

9、ificTranscriptionFactorsandTranscriptionalRegulation特异转录因子与转录调控特异转录因子与转录调控4.4.1Activators/激活蛋白激活蛋白4.4.2Repressors/阻遏蛋白阻遏蛋白34/764.4.1Activators/激活蛋白激活蛋白Specifictranscriptionfactorsthatenhancetherateoftranscriptionarecalledactivators.能提高转录速率能提高转录速率的特异转录因子的特异转录因子称为称为激活蛋白激活蛋白。1.Helprecruitthepre-initiat

10、ioncomplex.2.Helporganizethesubunitsofthepre-initiationcomplex,andmaintaincohesionofthecomplex.3.AttractenzymestoloosenDNAfromproteins,freeingimportantregionslikethepromoter.35/761.Helprecruitthepre-initiationcomplex36/762.Helporganizethesubunitsofthepre-initiationcomplex37/763.Attractenzymestoloose

11、nDNA38/764.4.2Repressors/阻遏蛋白阻遏蛋白Specifictranscriptionfactorsthatpreventthetranscriptionofagenearecalledrepressors.能阻碍基因转录能阻碍基因转录的特异转录因子的特异转录因子称为称为阻遏蛋白阻遏蛋白。1.Blockingtheactivityofactivators.2.Blockingaccessofthepre-initiationcomplextothepromoter.3.RecruitingenzymesthattightenDNAaroundproteins.39/761

12、.Blockingtheactivityofactivators40/762.Blockingaccessofthepre-initiationcomplextothepromoter.41/763.RecruitingenzymesthattightenDNAaroundproteins42/764.4.3EnhancersandSilencers增强子和沉默子增强子和沉默子SpecifictranscriptionfactorsrelyonDNAsequencestotellthemhoweachgeneshouldberegulated.Thesesequencesarecalleden

13、hancersorsilencers,dependingwhethertheybindactivatorsorrepressors,respectively.特异转录因子依靠特异转录因子依靠DNA序列来告诉它序列来告诉它们应该怎样调控每们应该怎样调控每一种基因。这些序一种基因。这些序列称为列称为增强子增强子或或沉沉默子默子，分别依赖于，分别依赖于它们结合的是激活它们结合的是激活蛋白还是阻遏蛋白。蛋白还是阻遏蛋白。43/76EnhancersandSilencersTranscriptionisactivatedEnhancerTranscriptionisrepressedSilencerRe

14、pressorActivator44/76DNAlooping/DNA成环成环45/76SeaUrchinEndo 16geneAredseaurchin红海胆红海胆46/764.5StructuresofSpecificTranscriptionFactors4.5特异转录因子的结构特异转录因子的结构?ProkaryoticEukaryotic47/76MajorGroovevs.MinorGrooveMajorgrooveATGCMinorgrooveATGC48/764.5.1DNA-BindingMotifsinProkaryotes原核生物原核生物DNA结合基序结合基序Recogni

15、tionhelixThehelix-turn-helix(HTH)motif49/76NegativeRegulationthelacRepressor负调控负调控lac阻遏蛋白阻遏蛋白50/76Show3DstructureofthelacrepressorFile:lacrepressorwithDNA.val51/76Thetrprepressor52/76ThetrprepressorTrpTrprepressorDNAE.coliOperator53/76Show3DstructureofthetrprepressorFile:trprepressor.val54/764.5.2DN

16、A-BindingMotifsineukaryote真核生物真核生物DNA结合基序结合基序1.Thehomeodomain同源异型域同源异型域2.Zincfingermotif锌指基序锌指基序3.Leucinezipper亮氨酸拉链亮氨酸拉链4.HLHmotif5.螺旋螺旋-环环-螺旋基序螺旋基序?Eukaryotic55/761.Thehomeodomain/同源异型同源异型域域SimilartoHTHofprokaryotes56/76MutationofhomeoticgenesHomeoticgenes57/76Show3DstructureofhomeodomainFile:Home

17、odomain.valBaird-TitusJM,etal.ThesolutionstructureofthenativeK50BicoidhomeodomainboundtotheconsensusTAATCCDNA-bindingsiteJ.Mol.Biol.v356,p.1137-115158/762.Zincfingermotif/锌指基序锌指基序59/76Show3DstructureofzincfingersFinger1Finger2Finger3File:Zincfinger.val60/763.Leucinezipper/亮氨酸拉链亮氨酸拉链Leucines61/76Hete

18、rodimerization/异源二聚化作用异源二聚化作用62/76Show3DstructureofleucinezipperWuSW,etal.DesignandcharacterizationofamultimericDNAbindingproteinusingSac7dandGCN4astemplatesProteins v60,p.617-628File:Leucinezipper.valYeastcellswww.zeiss.de/C12567BE0045ACF1/ContentsWWWInte63/764.Helix-loop-helixmotif/螺旋螺旋-环环-螺旋基螺旋基序

19、序Thehelix-loop-helix(HLH)motif64/76HLHversusHTHThehelix-loop-helix(HLH)motifThehelix-turn-helix(HTH)motif65/76Show3DstructureofHLHFerre-DAmareAR,etal.RecognitionbyMaxofitscognateDNAthroughadimericb/HLH/ZdomainNature v363,p.38-45File:HLH.val66/764.6Experiments/实验研究实验研究5.5.1RNApolymerasetargetsRNA聚合酶的

20、目标聚合酶的目标5.5.2ModularityofSpecificTranscriptionFactors特异转录因子的模块化特异转录因子的模块化67/764.6.1RNApolymerasetargetsRNA聚合酶的目标聚合酶的目标68/76-amanitin/鹅膏蕈碱鹅膏蕈碱69/76Whyis-amanitinpoisonous?70/76FunctionsofRNApolymerasesRNApolymeraseIRNApolymeraseIIRNApolymeraseIIIrRNAprecursorHighconcentrationof-amanitinRNApolymeraseI

21、producesrRNAprecursors.71/76FunctionsofRNApolymerasesRNApolymeraseIRNApolymeraseIIRNApolymeraseIIIrRNAprecursortRNA,5SrRNALowconcentrationof-amanitinRNApolymeraseIIIproducestRNA,5SrRNAandothersnRNAs.72/764.6.2ModularityofSpecificTranscriptionFactors特异转录因子的模块化特异转录因子的模块化Moduleexchange73/76Thereportergenes/报告基因报告基因physicalsciences.ucsd.edu/outreach/image_gall.www.bio- Brain cancer modelsHumanU-87-RFPgliomagrowinginbrainofnudemouse.脑瘤模型：生长在裸鼠脑中的人神经胶质瘤脑瘤模型：生长在裸鼠脑中的人神经胶质瘤 RFPGFP74/76ThemodularityofGal475/76ThemodularityofGal476/76ThemodularityofGal4