title: Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression.
abstract: Transcriptional repression by Mad-Max heterodimers requires interaction of Mad with the corepressors mSin3A/B. Sin3p, the S. cerevisiae homolog of mSin3, functions in the same pathway as Rpd3p, a protein related to two recently identified mammalian histone deacetylases, HDAC1 and HDAC2. Here, we demonstrate that mSin3A and HDAC1/2 are associated in vivo. HDAC2 binding requires a conserved region of mSin3A capable of mediating transcriptional repression. In addition, Mad1 forms a complex with mSin3 and HDAC2 that contains histone deacetylase activity. Trichostatin A, an inhibitor of histone deacetylases, abolishes Mad repression. We propose that Mad-Max functions by recruiting the mSin3-HDAC corepressor complex that deacetylates nucleosomal histones, producing alterations in chromatin structure that block transcription.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Laherty
authors.forename: W M
authors.initials: WM
authors.lastname: Yang
authors.forename: J M
authors.initials: JM
authors.lastname: Sun
authors.forename: J R
authors.initials: JR
authors.lastname: Davie
authors.forename: E
authors.initials: E
authors.lastname: Seto
authors.forename: R N
authors.initials: RN
authors.lastname: Eisenman
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D011817:Rabbits; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D006655:Histone Deacetylases