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ID:40704183
大小:6.98 MB
页数:90页
时间:2019-08-06
《13_Transcriptional regulation_Regulatory RNA & Techniques》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、MolecularBiology,2016SpringTranscriptionalRegulationṷᙯ2016/5/17NucleosomemodifiersTwotypes✦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
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