CREB-binding Protein/p300 Activates MyoD by Acetylation

• Published in: The Journal of biological chemistry Vol. 275; no. 44; pp. 34359 - 34364
• Main Authors: Polesskaya, Anna, Duquet, Arnaud, Naguibneva, Irina, Weise, Christoph, Vervisch, Arlette, Bengal, Eyal, Hucho, Ferdinand, Robin, Philippe, Harel-Bellan, Annick
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.11.2000; American Society for Biochemistry and Molecular Biology
• Subjects: Acetylation; Acetyltransferases - metabolism; Amino Acid Sequence; Animals; CREB-binding protein; E1A-Associated p300 Protein; Histone Acetyltransferases; Mice; Mice, Inbred C3H; Molecular Sequence Data; MyoD protein; MyoD Protein - metabolism; Nuclear Proteins - metabolism; p300 protein; PCAF protein; Saccharomyces cerevisiae Proteins; Trans-Activators - metabolism; Transcriptional Activation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M003815200

The myogenic protein MyoD requires two nuclear histone acetyltransferases, CREB-binding protein (CBP)/p300 and PCAF, to transactivate muscle promoters. MyoD is acetylated by PCAFin vitro, which seems to increase its affinity for DNA. We here show that MyoD is constitutively acetylated in muscle cells.In vitro, MyoD is acetylated both by CBP/p300 and by PCAF on two lysines located at the boundary of the DNA binding domain. MyoD acetylation by CBP/p300 (as well as by PCAF) increases its activity on a muscle-specific promoter, as assessed by microinjection experiments. MyoD mutants that cannot be acetylated in vitro are not activated in the functional assay. Our results provide direct evidence that MyoD acetylation functionally activates the protein and show that both PCAF and CBP/p300 are candidate enzymes for MyoD acetylationin vivo.