Factors That Promote H3 Chromatin Integrity during Transcription Prevent Promiscuous Deposition of CENP-ACnp1 in Fission Yeast 英文参考文献.docVIP

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Factors That Promote H3 Chromatin Integrity during Transcription Prevent Promiscuous Deposition of CENP-ACnp1 in Fission Yeast 英文参考文献.doc

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Factors That Promote H3 Chromatin Integrity during Transcription Prevent Promiscuous Deposition of CENP-ACnp1 in Fission Yeast 英文参考文献

FactorsThatPromoteH3ChromatinIntegrityduring TranscriptionPreventPromiscuousDepositionofCENP- ACnp1 inFissionYeast EunShikChoi1¤a,AnnelieStra?lfors2,SandraCatania1,AraceliG.Castillo1¤b,J.PeterSvensson2, AlisonL.Pidoux1,KarlEkwall2,RobinC.Allshire1* 1WellcomeTrustCentreforCellBiology,SchoolofBiologicalSciences,TheUniversityofEdinburgh,Edinburgh,Scotland,UnitedKingdom,2DepartmentofBiosciences andNutrition,KarolinskaInstitutet,NOVUM,Huddinge,Sweden Abstract SpecializedchromatincontainingCENP-AnucleosomesinsteadofH3nucleosomesisfoundatallcentromeres.However, the mechanisms that specify the locations at which CENP-A chromatin is assembled remain elusive in organisms with regional,epigeneticallyregulatedcentromeres.ItisknownthatnormalcentromericDNAistranscribedinseveralsystems including the fission yeast, Schizosaccharomyces pombe. Here, we show that factors which preserve stable histone H3 chromatinduringtranscriptionalsoplayaroleinpreventingpromiscuousCENP-ACnp1depositioninfissionyeast.Mutations inthehistonechaperoneFACTimpairthemaintenanceofH3chromatinontranscribedregionsandpromotewidespread CENP-ACnp1 incorporation at non-centromeric sites. FACT has little or no effect on CENP-ACnp1 assembly at endogenous centromereswhereCENP-ACnp1 isnormallyassembled.Incontrast,Clr6complexII(Clr6-CII;equivalenttoRpd3S)histone deacetylasefunctionhasamoresubtleimpactonthestabilityoftranscribedH3chromatinandactstopreventtheectopic accumulationofCENP-ACnp1atspecificloci,includingsubtelomericregions,whereCENP-ACnp1ispreferentiallyassembled. Moreover,defectiveClr6-CIIfunctionallowsthedenovoassemblyofCENP-ACnp1chromatinoncentromericDNA,bypassing thenormalrequirementforheterochromatin.Thus,ouranalysesshowthatalterationsintheprocessofchromatinassembly duringtranscriptioncandestabilizeH3nucleosomesandtherebyallowCENP-ACnp1 toassembleinitsplace.Wepropose thatnormalcentromeresprovideaspecificchromatincontextthatlimitsreassemblyofH3chromatinduringtranscription and thereby promotes the est