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THEJOURNALOFBIOLOGICALCHEMISTRYVol.280,No.12,IssueofMarch25,pp.11987–11994,2005©2005byTheAmericanSocietyforBiochemistryandMolecularBiology,Inc.PrintedinU.S.A.CharacterizationoftheYeastTrimeric-SASAcetyltransferaseComplex*Receivedforpublication,January7,2005Published,JBCPapersinPress,January18,2005,DOI10.1074/jbc.M500276200Wei-JongShia‡§,ShigehiroOsada¶,LaurenceFlorens‡,SeleneK.Swanson‡,MichaelP.Washburn‡,andJerryL.Workman‡ʈFromthe‡StowersInstituteforMedicalResearch,KansasCity,Missouri64110,the§DepartmentofBiochemistryandMolecularBiology,ThePennsylvaniaStateUniversity,UniversityPark,Pennsylvania16802-4500,andthe¶LaboratoryofEnvironmentalBiochemistry,GraduateSchoolofPharmaceuticalSciences,OsakaUniversity,1-6Yamada-Oka,Suita,Osaka565-0871,JapanTheyeastSAS2(SomethingAboutSilencing2)geneatHMLinsir1⌬background(3).IthasalsobeenreportedthatencodesamemberoftheMYSTproteinfamilyofhistoneSAS2regulatessilencingdifferentlyatdifferentloci.SAS2acetyltransferases(HATs)andisinvolvedintranscrip-functionsasapositiveregulatoratHMLandtelomeres(3);itstionalsilencingatallsilentloci(HML,HMR,telomeres,deletionleadstolossofsilencingattheseloci.Oppositely,andrDNA)inSaccharomycescerevisiae.Sas2isthecat-deletionofSAS2enhancesrDNAsilencing(4)andrestoresthealyticsubunitofayeasthistoneacetyltransferasecom-silencingdefectsatHMRwithamutatedsilencer(5).Notably,plextermedSAScomplex.TheenzymaticactivityofSASlossofSAS2doesnotaffectsilencingatwild-typeHMRmatingcomplexonfreehistoneshasbeenreported,butnucleo-locus.TheexactmechanismsforSas2-mediatedsilencingatsomalHATactivityhasnotyetbeendocumented.Heredifferentlociremainunclear.GeneticevidenceshowedthatweshowthatthenativeyeastSAScomplexisasmalltwoothergenes,termedSAS4andSAS5,sharethesametrimericproteincomplexcomposedsolelyofSas2,Sas4,regulatoryfunctionsinsilencingwithSAS2andmayfunctionandSas5withamolecularmassofabout125kDa.ItisinthesamegeneticpathwaywithSAS2(6,7).capableofacetylatingbothfreehistonesandnucleo-Sas2isamemberoftheM
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