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1、artICleSDnmt1andDnmt3amaintainDNAmethylationandregulatesynapticfunctioninadultforebrainneuronsJianFeng1,YuZhou2,6,SusanLCampbell3,ThucLe1,4,EnLi5,JDavidSweatt3,AlcinoJSilva2&GuopingFan1Dnmt1andDnmt3aareimportantDNAmethyltransferasesthatareexpressedinpostmitot
2、icneurons,buttheirfunctionintheCNSisunclear.WegeneratedconditionalmutantmicethatlackDnmt1,Dnmt3aorbothexclusivelyinforebrainexcitatoryneuronsandfoundthatonlydoubleknockout(DKO)miceshowedabnormallong-termplasticityinthehippocampalCA1regiontogetherwithdeficitsi
3、nlearningandmemory.Althoughwefoundnoneuronalloss,hippocampalneuronsinDKOmiceweresmallerthaninthewildtype;furthermore,DKOneuronsshowedderegulatedexpressionofgenes,includingtheclassIMHCgenesandStat1,thatareknowntocontributetosynapticplasticity.Inaddition,weobse
4、rvedasignificantdecreaseinDNAmethylationinDKOneurons.WeconcludethatDnmt1andDnmt3aarerequiredforsynapticplasticity,learningandmemorythroughtheiroverlappingrolesinmaintainingDNAmethylationandmodulatingneuronalgeneexpressioninadultCNSneurons.Thelong-lastingchang
5、esinsynapticplasticitythatunderlielearningtransmission12,13.Althoughthesestudiesprovideampleevidencethatandmemoryrequirechangesinneuronalgeneexpression.EpigeneticDNAmethylationisessentialinneuronaldevelopmentandfunc-mechanismssuchashistonemodification1andDNAm
6、ethylationaretion,theydonotrevealtheroleofcontinuousDnmtexpressioninthoughttocontributetothisadaptiveneuronalgeneexpression2–5.postmitoticneurons.Indeed,ourstudyofconditionalDnmt1geneDifferenthistonemodificationsareassociatedwithvariousneuro-deletioninpostmit
7、oticCNSneuronsfailedtorevealanyobviousnalgeneexpressionstates1;moreover,increasinghistoneacetylationneuronalphenotypes,suchasalossofDNAmethylationinculturedbytreatmentwithhistonedeacetylaseinhibitorspromotesrecoverycerebellarneuronsorcorticalandhippocampalneu
8、ronsinvivo11.oflearningandmemoryinamousemodelofneurodegeneration6.Nevertheless,wedidobserveamoderateeffectoncorticalneuronalHowever,thefunctionofDNAmethylationintheadultnervoussurvivalina
