2011-nrg-Enhancer function-new insights into the regulation of tissue-specific gene expression

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1、REVIEWSMODESOFTRANSCRIPTIONALREGULATIONEnhancerfunction:newinsightsintotheregulationoftissue-specificgeneexpressionChin‑TongOngandVictorG. CorcesAbstract

2、Enhancerfunctionunderliesregulatoryprocessesbywhichcellsestablishpatternsofgeneexpression.Recentresultssuggestthatmanyenhancersaresp

3、ecifiedbyparticularchromatinmarksinpluripotentcells,whichmaybemodifiedlaterindevelopmenttoalterpatternsofgeneexpressionandcelldifferentiationchoices.Thesemarksmaycontributetotherepertoireofepigeneticmechanismsresponsibleforcellularmemoryanddeterminethetimingoftranscriptionfactoraccessi

4、bilitytotheenhancer.Mechanistically,cohesinandnon-codingRNAsareemergingascrucialplayersresponsibleforfacilitatingenhancer–promoterinteractionsatsomegenes.Surprisingly,theseinteractionsmayberequirednotonlytofacilitateinitiationoftranscriptionbutalsotoactivatethereleaseofRNApolymeraseII(

5、RNAPII)frompromoter-proximalpausing.Differentiationofthevariouscelltypespresentinthis,enhancer-boundtranscriptionfactorsloopouttheMediatorThe~30‑subunitco‑activatormulticellularorganismsrequirestheestablishmentinterveningsequencesandcontactthepromoterregion,complexthatisnecessaryofspat

6、iotemporalpatternsofgeneexpressionduringexplainingtheabilityofenhancerstoactinadistance-forsuccessfultranscriptionatdevelopment1.Transcriptionofeukaryoticgenesisanindependentfashion8(FIG.1).ActivationofeukaryoticclassIIpromotersofmetazoansexceedinglyintricateprocessthatrequiresthepreci

7、segenesrequires,inaddition,decompactionofthechroma-genes.Mediatorcoordinatesorchestrationofacomplexsetofinteractionsamongtinfibre.Thistaskisalsocarriedoutbyenhancer-boundthesignalsbetweenenhancersamyriadofproteinsandDNAsequences2(FIG.1).transcriptionfactorsthatcanrecruithistonemodifyin

8、gandthegeneraltranscriptionmachinerythroughitsRegulationoftranscriptionisaccomplishedmainlybyenzymesorATP-dependentchromatinremodellinginteractionwithRNAenhancers,whichareDNAsequencescontainingmul-complexestoalterchromatinstructureandincreasethepolymeraseIIandtiplebindingsitesforavar