Interaction between acetylated MyoD and the bromodomain of CBP and/or p300.
Acetylation is emerging as a posttranslational modification of nuclear proteins 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 that acetylation increases the affinity of myogenic factor MyoD for acetyltransferases CBP and p300. In myogenic cells, the fraction of endogenous MyoD that is acetylated was found associated with CBP or p300. In vitro, the interaction between MyoD and CBP was more resistant to high salt concentrations and was detected with lower doses of MyoD when MyoD was acetylated. Interestingly, an analysis of CBP mutants revealed that the interaction with acetylated MyoD involves the bromodomain of CBP. In live cells, MyoD mutants that cannot be acetylated did not associate with CBP or p300 and were strongly impaired in their ability to cooperate with CBP for transcriptional activation of a muscle creatine kinase-luciferase construct. Taken together, our data suggest a new mechanism for activation of protein function by acetylation and demonstrate for the first time an acetylation-dependent interaction between the bromodomain of CBP and a nonhistone protein.
Polesskaya
A
A
Laboratoire Oncogenèse, Différenciation et Transduction du Signal, CNRS UPR 9079, Institut André Lwoff, Villejuif, France.
Naguibneva
I
I
Duquet
A
A
Bengal
E
E
Robin
P
P
Harel-Bellan
A
A
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D051548:Histone Acetyltransferases; D017570:MyoD Protein / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D013379:Substrate Specificity; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D017570:MyoD Protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor