title: A feed-forward repression mechanism anchors the Sin3/histone deacetylase and N-CoR/SMRT corepressors on chromatin.
abstract: Transcription in eukaryotes is governed in part by histone acetyltransferase (HAT)- and histone deacetylase (HDAC)-containing complexes that are recruited via activators and repressors, respectively. Here, we show that the Sin3/HDAC and N-CoR/SMRT corepressor complexes repress transcription from histone H3- and/or H4-acetylated nucleosomal templates in vitro. Repression of histone H3-acetylated templates was completely dependent on the histone deacetylase activity of the corepressor complexes, whereas this activity was not required to repress H4-acetylated templates. Following deacetylation, both complexes become stably anchored in a repressor-independent manner to nucleosomal templates containing hypoacetylated histone H3, but not H4, resulting in dominance of repression over activation. The observed stable anchoring of corepressor complexes casts doubt on the view of a dynamic balance between readily exchangeable HAT and HDAC activities regulating transcription and implies that pathways need to be in place to actively remove HDAC complexes from hypoacetylated promoters to switch on silent genes.
authors.affiliation: NCMLS, Radboud University Nijmegen, Department of Molecular Biology, Geert Grooteplein Zuid 30, Nijmegen, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Vermeulen
authors.forename: Wendy
authors.initials: W
authors.lastname: Walter
authors.forename: Xavier
authors.initials: X
authors.lastname: Le Guezennec
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Kim
authors.forename: Rajeswari S
authors.initials: RS
authors.lastname: Edayathumangalam
authors.forename: Edwin
authors.initials: E
authors.lastname: Lasonder
authors.forename: Karolin
authors.initials: K
authors.lastname: Luger
authors.forename: Robert G
authors.initials: RG
authors.lastname: Roeder
authors.forename: Colin
authors.initials: C
authors.lastname: Logie
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Berger
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005246:Feedback; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic; D014981:Xenopus
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; C539127:NCOR1 protein, human; C539130:NCOR2 protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D009707:Nucleosomes; D012097:Repressor Proteins; D004247:DNA; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex