原核生物基因表达调控Regulation of Gene Expression in Prokaryotes 08

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1、DuanMa,Ph.D.,M.D.ProfessorandDeputyDirectorKeyLabofMolecularMedicine,MinistryofEducation.ResearchCenterforBirthDefects.ChapterXIIIRegulationofGeneExpressioninProkaryotes原核生物基因表达调控WhyGeneRegulationofExpression?GeneexpressionhastemporalspecificityandspatialspecificityGeneexpression

2、hasphysiologicalspecificityandpathologicalspecificityPreventionandtreatmentofdiseasesarerelatedwithgeneregulationFrançoisJacobMarkPtashneAndreLwoffWalterGilbertJacquesMonod1940-1950:AndreLwoff,E.coli,Phage,Lysogen,Lysis1961:JacobandMonod,Operon,Lactose,β-galactosidase1970:MarkP

3、tashneandGilbert,GeneRepression.1981:CharlesYanofsky,TrpOperon,Attenuation.CharlesYanofskyRegulationPointsofGeneExpressionChromatinactivationInitiation,elongationandterminationoftranscriptionInitiationisTranslationthekeypointofregulationProcessingandModificationofTranslationcis-ac

4、tingelementInitiationPointGeneBACodingsequenceproteinAproteinBtrans-actingfactorTranscriptionfactorTransregulationGeneaRNAABProteinAAcis-actingsitetrans-actingproductsStructuralgeneCcGenemRNACisregulationPositiveregulationCProteinCNegativeregulationGeneClusterTheOperonofBacteria细菌操

5、纵子StructureofLacOperonRegAreaStructuregeneDNAIPOzyaz：β-galactosidaseIgeneOperatory：permeasePromotera：transacetylaseCAPbindingsiteOptimalPromoterTTGACATATAAT828478655445809545605096LacOperonIsBlockedByRepressorProteinRepressorgeneDNAIPpolOzyamRNARepressorWithoutlactoseProteinLactose

6、OperonOpensByInducerDNAIpolPOzyaInitiatemRNATranscriptionmRNAβ-galactosidaseRepressorProteinLactoseGalactoseLactoseLacOperonIsRegulatedBycAMP-CAPPositivelylacTTTACANTATGTTA17N6TTGACATATAAT•LacoperonisweakpromoterandactivatedbyAMP-CAPafterbindingwithRNApoly.CAPbindingsiteDNAPOZYA+++

7、+TranscriptionCAPCAPCAPCAPCAPCAPcAMPishigh,withoutglucoseCAPcAMPislowandhaveglucoseLowgalactoseHighgalactoseGlucoselowcAMPhighRNA-polＩOONotranscriptionmRNAGlucosehighcAMPlowＩOONotranscriptionLowtranscriptionPrincipalofTrpOperonRegAreaStructureGenetrpRRNAPolyPORNAPolyLowTrpmRNAHighT

8、rpTrpRegulationoftranslati