Gene-X-ppt(Gene10-基因十)--Chapter28

Chapter28EukaryoticTranscriptionRegulation28.1Introduction•Eukaryoticgeneexpressionisusuallycontrolledatthelevelofinitiationoftranscriptionbyopeningthechromatin.FIGURE01:Geneexpressionpassesthroughmanystages28.1Introduction•epigenetic–Changesthatinfluencethephenotypewithoutalteringthegenotype.–Theyconsistofchangesinthepropertiesofacellthatareinherited,butthatdonotrepresentachangeingeneticinformation.28.2MechanismofActionofActivatorsandRepressors•Activatorsdeterminethefrequencyoftranscription.•repressor–Aproteinthatinhibitsexpressionofagene.–ItmayacttopreventtranscriptionbybindingtoanoperatorsiteinDNAortopreventtranslationbybindingtoRNA.28.2MechanismofActionofActivatorsandRepressors•positivecontrol–Thedefaultstateofgenesthatareunderpositivecontrolisthattheycannotbeexpressedunlessapositiveregulatorisbound.•trueactivator–Apositivetranscriptionfactorthatfunctionsbymakingcontact,directorindirect,withthebasalapparatustoactivatetranscription.28.2MechanismofActionofActivatorsandRepressorsFIGURE02:Transcriptionfactorsareactivatedinseveralways.28.2MechanismofActionofActivatorsandRepressors•Activatorsworkbymakingprotein–proteincontactswiththebasalfactors.•Activatorsmayworkviacoactivators.•Activatorsareregulatedinmanydifferentways.•antirepressor–Apositiveregulatorthatfunctionsinopeningchromatin.28.2MechanismofActionofActivatorsandRepressors•architecturalprotein–Aproteinthat,whenboundtoDNA,canalteritsstructure(e.g.,introduceabend).–Architecturalproteinsmayhavenootherfunction.FIGURE03:ArchitecturalproteinscontrolthestructureofDNA28.2MechanismofActionofActivatorsandRepressors•negativecontrol–Thedefaultstateofgenesthatareundernegativecontrolistobeexpressed.–Aspecificinterventionisrequiredtoturnthemoff.28.2MechanismofActionofActivatorsandRepressorsFIGURE04:Transcriptionfactorsactasrepressorsinseveralways.28.2MechanismofActionofActivatorsandRepressors•Somecomponentsofthetranscriptionalapparatusworkbychangingchromatinstructure.•Repressionisachievedbyaffectingchromatinstructureorbybindingtoandmaskingactivators.28.3IndependentDomainsBindDNAandActivateTranscription•DNA-bindingandtranscription-activationactivitiesarecarriedbyindependentdomainsofanactivator.•TheroleoftheDNA-bindingdomainistobringthetranscription-activationdomainintothevicinityofthepromoter.FIGURE05:Anactivatorhasindependentdomains28.4TheTwo-HybridAssayDetectsProtein–ProteinInteractions•Thetwo-hybridassayworksbyrequiringaninteractionbetweentwoproteins,whereonehasaDNA-bindingdomainandtheotherhasatranscription-activationdomain.FIGURE06:Two-hybridassaymeasureproteininteraction28.5ActivatorsInteractwiththeBasalApparatus•TheprinciplethatgovernsthefunctionofallactivatorsisthataDNA-bindingdomaindeterminesspecificityforthetargetpromoterorenhancer.•TheDNA-bindingdomainisresponsibleforlocalizingatranscription-activatingdomainintheproximityofthebasalapparatus.•AnactivatorthatworksdirectlyhasaDNA-bindingdomainandanactivatingdomain.28.5ActivatorsInteractwiththeBasalApparatus•Anactivatorthatdoesnothaveanactivatingdomainmayworkbybindingacoactivatorthathasanactivatingdomain.•Severalfactorsinthebasalapparatusaretargetswithwhichactivatorsorcoactivatorsinteract.FIGURE07:Anactivatormayuseacoactivator28.5ActivatorsInteractwiththeBasalApparatus•RNApolymerasemaybeassociatedwithvariousalternativesetsoftranscriptionfactorsintheformofaholoenzymecomplex.FIGURE09:RNApolymeraseexistsasaholoenzyme28.5ActivatorsInteractwiththeBasalApparatus•mediator–AlargeproteincomplexassociatedwithyeastbacterialRNApolymeraseII.–Itcontainsfactorsthatarenecessaryfortranscriptionfrommanyormostpromoters.28.6ThereAreManyTypesofDNA-BindingDomains•ActivatorsareclassifiedaccordingtothetypeofDNA-bindingdomain.•MembersofthesamegrouphavesequencevariationsofaspecificmotifthatconferspecificityforindividualDNAtargetsites.•zincfinger–ADNA-bindingmotifthattypifiesaclassoftranscriptionfactor.FIGURE10:TheZnfingerisaDNA-bindingmotif28.6ThereAreManyTypesofDNA-BindingDomains•steroidreceptor–Transcriptionfactorsthatareactivatedbybindingofasteroidligand.•helix-turn-helix–Themotifthatdescribesanarrangementoftwoα-helicesthatformasitethatbindstoDNA,onefittingintothemajorgrooveofDNAandtheotherlyingacrossit.•homeodomain–ADNA-bindingmotifthattypifiesaclassoftranscriptionfactors.FIGURE12:Thehomeodomainhasthreehelices28.6ThereAreManyTypesofDNA-BindingDomains•helix-loop-helix–ThemotifthatisresponsiblefordimerizationofaclassoftranscriptionfactorscalledHLHproteins.–AbHLHproteinhasabasicDNA-bindingsequenceclosetothedimerizationmotif.FIGURE13:HLHproteinsformtwosortsofdimers28.6ThereAreManyTypesofDNA-BindingDomains•leucinezipper–Adimerizationmotifthatisfoundinaclassoftranscriptionfactors.•bZIP–AbZIP(basiczipper)proteinhasabasicDNA-bindingregionadjacenttoaleucinezipperdimerizationmotif.FIGURE14:Leucinezippersdimerize28.7ChromatinRemodelingIsanActiveProcess•chromatinremodeling–Theenergy-dependentdisplacementorreorganizationofnucleosomesthatoccursinconjunctionwithactivationofgenesfortranscription.FIGURE15:Chromatinstructureisstable28.7ChromatinRemod