Acetylation of MyoD directed by PCAF is necessary for the execution of themuscle program

p300/CBP and PCAF coactivators have acetyltransferase activites and regulat e transcription, cell cycle progression, and differentiation. They are both required for MyoD activity and muscle differentiation. Nevertheless, their roles must be different since the acetyltransferase activity of PCAF but n ot of p300 is involved in controlling myogenic transcription and differenti ation. Here, we provide a molecular explanation of this phenomenon and repo rt that MyoD is directly acetylated by PCAF at evolutionarily conserved lys ines. Acetylated MyoD displays an increased affinity for its DNA target. Im portantly, conservative substitutions of acetylated lysines with nonacetyla table arginines impair the ability of MyoD to stimulate transcription and t o induce muscle conversion indicating that acetylation of MyoD is functiona lly critical.