RNF12 Activates Xist and Is Essential for X Chromosome Inactivation 英文参考文献.docVIP

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RNF12 Activates Xist and Is Essential for X Chromosome Inactivation 英文参考文献.doc

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RNF12 Activates Xist and Is Essential for X Chromosome Inactivation 英文参考文献

RNF12ActivatesXistandIsEssentialforXChromosome Inactivation TahsinStefanBarakat1,NilhanGunhanlar1,CristinaGontanPardo1,EskeatnafMulugetaAchame1, MehrnazGhazvini1,2,RubenBoers1,AnnegienKenter1,EvelineRentmeester1,J.AntonGrootegoed1, JoostGribnau1* 1Department of Reproduction and Development, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, 2Erasmus Stem Cell Institute, Erasmus MC, UniversityMedicalCenter,Rotterdam,TheNetherlands Abstract Insomaticcellsoffemaleplacentalmammals,oneofthetwoXchromosomesistranscriptionallysilencedtoaccomplishan equal dose of X-encoded gene products in males and females. Initiation of random X chromosome inactivation (XCI) is thoughttoberegulatedbyX-encodedactivatorsandautosomallyencodedsuppressorscontrollingXist.SpreadingofXist RNAleadstosilencingoftheXchromosomeincis.Here,wedemonstratethatthedosedependentX-encodedXCIactivator RNF12/RLIMactsintransandactivatesXist.WedidnotfindevidenceforRNF12-mediatedregulationofXCIthroughTsixor theXistintron1region,whicharebothknowntobeinvolvedininhibitionofXist.Inaddition,wefoundthatXistintron1, whichcontainsapluripotencyfactorbindingsite,isnotrequiredforsuppressionofXistinundifferentiatedEScells.Analysis of female Rnf122/2 knockout ES cells showed that RNF12 is essential for initiation of XCI and is mainly involved in the regulationofXist.WeconcludethatRNF12isanindispensablefactorinup-regulationofXisttranscription,therebyleading toinitiationofrandomXCI. Citation: Barakat TS, Gunhanlar N, Gontan Pardo C, Mulugeta Achame E, Ghazvini M, et al. (2011) RNF12 Activates Xist and Is Essential for X Chromosome Inactivation.PLoSGenet7(1):e1002001.doi:10.1371/journal.pgen.1002001 Editor:WolfReik,TheBabrahamInstitute,UnitedKingdom ReceivedOctober8,2010;AcceptedNovember20,2010;PublishedJanuary27,2011 Copyright: ? 2011 Barakat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninany