NRSF-REST is required in vivo for repression of multiple neuronal target genes during embryogenesis

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1、articleNRSF/RESTisrequiredinvivoforrepressionofmultipleneuronaltargetgenesduringembryogenesisZhou-FengChen1*,AliceJ.Paquette2*&DavidJ.Anderson1,2*Z.-F.C.&A.J.P.contributedequallytothiswork.Theneuron-restrictivesilencerfactorNRSF(alsoknownasRESTandXBR)cansilencetranscriptionfromneuronalpromote

2、rsinnon-neuronalcelllines,butitsfunctionduringnormaldevelopmentisunknown.Inmice,atargetedmutationofRest,thegeneencodingNRSF,causedderepressionofneuron-specifictubulininasubsetofnon-neuraltissuesandembryoniclethality.MosaicinhibitionofNRSFinchickenembryos,usingadominant-negativeformofNRSF,alsoc

3、ausedderepressionofneuronaltubulin,aswellasofseveralotherneuronaltargetgenes,inbothnon-neuraltissuesandcentralnervoussystemneuronalprogenitors.TheseresultsindicatethatNRSFisrequiredtorepressneuronalgeneexpressioninvivo,inbothextra-neuralandundifferentiatedneuraltissue.IntroductionHerewehaveus

4、edtwoindependentandcomplementaryTheexpressionofcelltype-specificterminaldifferentiationgenesapproachestoassesstherequirementofNRSFforrepressionofisthoughttodependonbothpositiveandnegativetranscrip-neuronalgeneexpressioninvivo:targetedmutagenesisofResttionalcontrols1,whichareimplementedthrougho

5、utacell’s(thegeneencodingNRSF)inmice,andmosaicinhibitionofdevelopmentalhistory.NumerousgeneticstudieshaveprovidedNRSFinchickenembryosusingaretrovirallytransduceddom-evidencethatcelltype-specifictranscriptionalactivatorsareinant-negativeformoftheprotein.Ourresultsindicatethatessentialcomponents

6、ofthisprocess,butmuchlessisknownNRSFisrequiredtorepressendogenousneuronaltargetgenesaboutthecontributionoftissue-specifictranscriptionalrepres-innon-neuronaltissues,andalsotorepressthesegenesinsors,especiallyinhighervertebrates2.Althoughcis-actingneuralprecursors.silencerelementshavebeenidenti

7、fiedbypromoteranalysisinnumeroustissue-specificstructuralgenes1,relativelyfewproteinsResultsthatinteractwithsuchsilencershavebeenisolatedandgeneti-TargeteddeletionofRestcallycharacterizedinvivo.Genetargetinginmouseembryonicstem(ES)cellswasusedt