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p300对小鼠胚胎干细胞分化和Nanog表达的调控作用.docx

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p300对小鼠胚胎干细胞分化和Nanog表达的调控作用 Abstract P300,asahistoneacetyltransferase,playsimportantrolesinregulatinggeneexpressionandvariouscellularprocesses.Recentstudieshaveshownthatp300isinvolvedinregulatingthedifferentiationofembryonicstemcells(ESCs)byaffectingtheexpressionofpluripotencyfactors.Inthisreview,wesummarizethecurrentknowledgeontheregulatoryroleofp300inthedifferentiationofmouseESCsandtheexpressionofNanog. Introduction Embryonicstemcells(ESCs)arepluripotentcellsthatcandifferentiateintoanycelltypeinthebody.TheregulationofESCdifferentiationisacomplexprocessthatinvolvestheactivationandrepressionofspecificgeneexpressionprograms.ThemaintenanceofESCpluripotencyinvolvestheinteractionofvarioustranscriptionalfactors,includingOct4,Sox2,andNanog,whichareresponsiblefortheactivationoftargetgenesrequiredformaintainingthepluripotentstate.However,thedifferentiationofESCsrequiresthesuppressionofthesefactorsandtheactivationofanewsetofgenesthatareresponsiblefortheformationofdifferentcelltypes. Severalstudieshaveshownthatthehistoneacetyltransferasep300playsanimportantroleintheregulationofESCdifferentiation.P300isatranscriptionalcoactivatorthatbindstospecifictranscriptionfactorsandpromoteschromatinremodelingthroughitsabilitytoacetylateand/ordeacetylatehistones,resultingintheactivationorrepressionofgeneexpression.Additionally,p300interactswithotherepigeneticmodifiers,suchasDNAmethyltransferasesandhistonemethyltransferases,toregulategeneexpressionandcellfatedecisions. P300andESCDifferentiation Severalstudieshaveshownthatp300isinvolvedinregulatingthedifferentiationofESCsbyaffectingtheexpressionofspecifictranscriptionfactors.Forexample,p300wasshowntobindtoandacetylateOct4,resultinginitsstabilizationandenhancedtranscriptionalactivity(1,2).Inaddition,p300wasshowntointeractwiththeWnt/β-cateninsignalingpathway,whichisrequiredforthedifferentiationofESCsintomesodermandendodermlineages.P300wasfoundtoacetylateβ-catenin,resultinginenhancedtranscriptionalactivityandtheactivationofWnttargetgenes(3). Fu