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1、TheEMBOJournalVol.21No.24pp.6820±6831,2002InvivodestabilizationofdynamicmicrotubulesbyHDAC6-mediateddeacetylation1,21,3pretedbymachinerycapableoflocallymodifyingtheAkihisaMatsuyama,TadahiroShimazu,YukoSumida1,2,AkikoSaito3,structureandfunctionofchromatin.Histo
2、neacetylationisYasuhiroYoshimatsu3,believedtoplayacentralroleinthis`histonecode'systemDaphneÂSeigneurin-Berny4,(Turner,1993).Manyhistoneacetyltransferases(HATs)52andhistonedeacetylases(HDACs)are,respectively,HiroyukiOsada,YasuhikoKomatsu,2,64activatorsandrepre
3、ssorsoftranscription(KuoandAllis,NorikazuNishino,SaadiKhochbin,31998).Besideschromatin-relatedfunctions,proteinSueharuHorinouchiand1,2,3,7acetylationseemstobeasignaldirectlycontrollingtheMinoruYoshidaactivityofkeycellularregulators(Kouzarides,2000).15HATsandHD
4、ACshavebeenshowntocontrolthestateofChemicalGeneticsLaboratory,AntibioticsLaboratory,RIKEN,2Wako,Saitama351-0198,CRESTResearchProject,JapanScienceacetylationofmanynon-histoneproteins,amongwhich3andTechnologyCorporation,Saitama332-0012,Departmentofsomearecytopla
5、smic(Kouzarides,2000;SternerandBiotechnology,TheUniversityofTokyo,Bunkyo-ku,Tokyo6Berger,2000).Althoughthesigni®canceofthenuclear113-8657,GraduateSchoolofLifeScienceandSystemsEngineering,KyushuInstituteofTechnology,Wakamatsu,Kitakyushu808-0196,proteinacetylati
6、onisunderintensiveinvestigation,almost4JapanandLaboratoiredeBiologieMoleÂculaireetCellulairedelanothingisknownaboutthecytoplasmicproteinacetyla-DiffeÂrenciation-INSERMU309,Equipe,ChromatineetExpressiondestion.However,allmembersofclassIIHDACsshowaGeÁnes,Institu
7、tAlbertBonniot,FaculteÂdeMeÂdecine,DomainedelaregulatedintracellularlocalizationandcouldbefoundinMerci,Franceboththecytoplasmandthenucleus(Khochbinetal.,7Correspondingauthor2001).ClassIIHDACsareenzymeswhosecatalytice-mail:yoshidam@postman.riken.go.jpdomainisre
8、latedtothatofyeasthistonedeacetylaseHDA1(Grozingeretal.,1999;Miskaetal.,1999;TrichostatinA(TSA)inhibitsallhistonedeacetylasesVerdelandKhochbin,1999;Wangetal.,1999;Kao(HDACs)ofbothc