13_Transcriptional regulation_Regulatory RNA & Techniques

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1、MolecularBiology,2016SpringTranscriptionalRegulationṷ෈ᙯ2016/5/17NucleosomemodifiersTwotypes✦thosethataddchemicalgroupstothetailsofhistones✦i.e.,histoneacetyltransferases(HATs)✦thosethatdisplace/remodelthenucleosomes✦i.e.,ATP-dependentactivityofSWI/SNFLocalalte

2、rationinchromatinstructuredirectedbyactivatorsHATs:1)loosenchromatinstructure,freeingupsitesfortranscription;2)helpbindingofthetranscriptionalmachinerybycreatingspecificbindingsitesonnucleosomesforproteinsbearingbromodomains.(i.e.,onecomponentoftheTFIIDcomplex

3、bearsbromodomains)ActivatorsrecruitadditionalfactorsneededforefficientinitiationorelongationatsomepromotersPausingandreleaseofPolIIGAGA-bindingfactorphosphorylateCTDofPolIIP-TEFbispartofSEC(SuperElongationComplex)FactsaboutpauseofRNAPolII✦Pausedpolymeraseismor

4、ecommonlyseenduringdevelopment✦Aboutone-thirdofallprotein-codinggenescontainpausedPolIIbeforetheiractivationduringdevelopment,i.e.,humanembryonicstemcellsandtheearlyDrosophilaembryo✦ItispossiblethatpausedPolIIisawayofexcludinginhibitorynucleosomesfromthepromo

5、terregion,renderingthepromoter“poised”forrapidactivationbyupstreamregulatorysequences✦ManyyeastpromoterscontainAT-richsequencesthatdiminishtheformationofnucleosomesActionatadistance:loopsandinsulators✦Ifanenhanceractivatesaspecificgene400kbaway,whatstopsitfrom

6、activatingothergeneswhosepromotersarewithinthatrange?✦Onaverage,becausethereisageneevery100–200kbinatypicalvertebrategenome,suchanenhancerhasto“choose”amongtwoormoregenes.✦Specificelementscalledinsulatorscontroltheactionsofactivators.Whenplacedbetweenanenhance

7、randapromoter,aninsulatorinhibitsactivationofthegenebythatenhancer.✦Theproteinsthatbindinsulatorsdonotactivelyrepressthepromoter,nordotheyinhibittheactivitiesoftheactivators.Rather,theyblockcommunicationbetweenthetwo.✦Insulatorsoftenbindalargezinc-fingerprotei

8、ncalledCTCF.ItisnowbelievedthatCTCFalsobindscohesinandthiscomplexformsachromosomalloopwiththenearestpromoter,therebyprecludingenhancersdistaltotheinsulatorfromformingasimilarloop.✦Cohesin