title: P300 transcriptional repression is mediated by SUMO modification.
abstract: p300 and CREB binding protein can both activate and repress transcription. Here, we locate the CRD1 transcriptional repression domain between residues 1017 and 1029 of p300. This region contains two copies of the sequence psiKxE that are modified by the ubiquitin-like protein SUMO-1. Mutations that reduce SUMO modification increase p300-mediated transcriptional activity and expression of a SUMO-specific protease or catalytically inactive Ubc9 relieved repression, demonstrating that p300 repression was mediated by SUMO conjugation. SUMO-modified CRD1 domain bound HDAC6 in vitro, and p300 repression was relieved by histone deacetylase inhibition and siRNA-mediated ablation of HDAC6 expression. These results reveal a mechanism controlling p300 function and suggest that SUMO-dependent repression is mediated by recruitment of HDAC6.
authors.affiliation: Institute of Biomolecular Sciences, University of Street Andrews, North Haugh, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Girdwood
authors.forename: Donna
authors.initials: D
authors.lastname: Bumpass
authors.forename: Owen A
authors.initials: OA
authors.lastname: Vaughan
authors.forename: Alison
authors.initials: A
authors.lastname: Thain
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Anderson
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Snowden
authors.forename: Elisa
authors.initials: E
authors.lastname: Garcia-Wilson
authors.forename: Neil D
authors.initials: ND
authors.lastname: Perkins
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Hay
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D022003:Cell Nucleus Structures / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000378:metabolism*; D005809:Genes, Regulator / Q000235:genetics*; D006367:HeLa Cells; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D025842:SUMO-1 Protein; C087628:TCEAL1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D008025:Ligases; D000098843:Ubiquitin-Conjugating Enzyme UBC9