真核基因表达调控Regulation of gene expression in eukaryotes 08

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1、GeneExpressioninEukaryotesRegulationofGeneExpressioninEukaryotes真核生物基因表达调控复旦大学分子医学教育部重点实验室马端13-16w24w25-28w9-12w29-32w8wFertilizationzygote4w7wRegulationPointsofGeneExpressionChromatinActivationTranscriptionPost-transcriptionalModificationRNATransportTranslationRNAdegradationP

2、ost-translationalmodificationsChromatinActivation染色质活化Chromatin-remodelingComplexes染色质重塑复合物Structureofnucleosome（核小体）ControlofTranscriptionInitiation转录起始调控UpstreamDownstreamInitiationenhancerexon1intron1intronnexonnPromoterTATAboxSilencerenhanceGCboxCAATboxrSomeCis-elementsinP

3、romotorTATAbox(TATAAAA)isat-25andisinvolvedinpositioningtheenzymeforcorrectinitiation.GCboxisat-90containsthesequenceGGGCGGandisrecognizedbythefactorSP1.CAATbox(CCAATCT)isat–75andisrecognizedbyalargegroupoftranscriptionfactorsandplaysastrongroleindeterminingtheefficiencyofthep

4、romoter.TranscriptionFactors（转录因子）Transcriptionfactor(sequence-specificDNAbindingfactor)isaproteinthatbindstospecificsequencesofDNAandtherebycontrolsthetransfer(ortranscription)ofgeneticinformationfromDNAtoRNA.GeneralTranscriptionFactorT7RNApolymeraseSpecificTranscriptionFacto

5、rTATAbindingproteinStructureofTranscriptionFactors•DNA-bindingdomain(DBD):attachtospecificsequencesofDNA.•Trans-activatingdomain(TAD):containbindingsitesforotherproteins.•glutamine-richactivationdomains•proline-richactivationdomains•acidicactivationdomains•Signalsensingdomain(

6、SSD)(ligandbindingdomain)whichsensesexternalsignalsandinresponsetransmitthesesignalstotherestofthetranscriptioncomplexresultinginupordownregulationofgeneexpression.•Protein-proteininteractiondomainBasichelix-loop-helix(bHLH)碱性螺旋－环－螺旋基序bHLHstructuralmotif(模体，基序）:twoαhelicesconn

7、ectedbyaloopStructuralmotif:apatterninaproteinstructureformedbythespatialarrangementofaminoacids.Ingeneral,transcriptionfactorsincludingthisdomainaredimeric,eachwithonehelixcontainingbasicaminoacidresiduesthatfacilitateDNAbinding.bHLHproteinstypicallybindtoaconsensussequenceca

8、lledanE-boxwhichisCACGTG,howeversomebHLHtranscriptionfactorsb