P300 transcriptional repression is mediated by SUMO modification

David Girdwood, Donna Bumpass, Owen A. Vaughan, Alison Thain, Lisa A. Anderson, Andrew W. Snowden, Elisa Garcia-Wilson, Neil D. Perkins, Ronald T. Hay

    Research output: Contribution to journalArticlepeer-review

    376 Citations (Scopus)


    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 ?KxE 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.
    Original languageEnglish
    Pages (from-to)1043-1054
    Number of pages12
    JournalMolecular Cell
    Issue number4
    Publication statusPublished - Apr 2003


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