Interaction between acetylated MyoD and the bromodomain of CBP and/or p300

Acetylation is emerging as a posttranslational modification of nuclear prot eins that is essential to the regulation of transcription and that modifies transcription factor affinity for binding sites on DNA, stability, and/or nuclear localization. Here, we present both in vitro and in vivo evidence t hat acetylation increases the affinity of myogenic factor MyoD for acetyltr ansferases CBP and p300. In myogenic cells, the fraction of endogenous MyoD that is acetylated was found associated with CBP or p300. In vitro, the in teraction between MyoD and CBP was more resistant to high salt concentratio ns and was detected with lower doses of MyoD when MyoD was acetylated. Inte restingly, an analysis of CBP mutants revealed that the interaction with ac etylated MyoD involves the bromodomain of CBP. In live cells, MyoD mutants that cannot be acetylated did not associate with CBP or p300 and were stron gly impaired in their ability to cooperate with CBP for transcriptional act ivation of a muscle creatine kinase-luciferase construct. Taken together, o ur data suggest a new mechanism for activation of protein function by acety lation and demonstrate for the first time an acetylation-dependent interact ion between the bromodomain of CBP and a nonhistone protein.