Acetylation of MyoD directed by PCAF is necessary for the execution of the muscle program.
p300/CBP and PCAF coactivators have acetyltransferase activities and regulate 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 not of p300 is involved in controlling myogenic transcription and differentiation. Here, we provide a molecular explanation of this phenomenon and report that MyoD is directly acetylated by PCAF at evolutionarily conserved lysines. Acetylated MyoD displays an increased affinity for its DNA target. Importantly, conservative substitutions of acetylated lysines with nonacetylatable arginines impair the ability of MyoD to stimulate transcription and to induce muscle conversion indicating that acetylation of MyoD is functionally critical.
Sartorelli
V
V
Institute for Genetic Medicine, University of Southern California, Los Angeles 90033, USA. sartorel@hsc.usc.edu
Puri
P L
PL
Hamamori
Y
Y
Ogryzko
V
V
Chung
G
G
Nakatani
Y
Y
Wang
J Y
JY
Kedes
L
L
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D051548:Histone Acetyltransferases; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D024510:Muscle Development; D009132:Muscles / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D017570:MyoD Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000235:genetics*
D004268:DNA-Binding Proteins; D017570:MyoD Protein; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D004247:DNA; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D008239:Lysine