Differential roles of p300 and PCAF acetyltransferases in muscle differentiation.
PCAF is a histone acetyltransferase that associates with p300/CBP and competes with E1A for access to them. While exogenous expression of PCAF potentiates both MyoD-directed transcription and myogenic differentiation, PCAF inactivation by anti-PCAF antibody microinjection prevents differentiation. MyoD interacts directly with both p300/CBP and PCAF, forming a multimeric protein complex on the promoter elements. Viral transforming factors that interfere with muscle differentiation disrupt this complex without affecting the MyoD-DNA interaction, indicating functional significance of the complex formation. Exogenous expression of PCAF or p300 promotes p21 expression and terminal cell-cycle arrest. Both of these activities are dependent on the histone acetyltransferase activity of PCAF, but not on that of p300. These results indicate that recruitment of histone acetyltransferase activity of PCAF by MyoD, through p300/CBP, is crucial for activation of the myogenic program.
Puri
P L
PL
Laboratory of Gene Expression, Fondazione Andrea Cesalpino, Istituto I Clinica Medica, Policlinico Umberto I, University of Rome, La Sapienza, Italy.
Sartorelli
V
V
Yang
X J
XJ
Hamamori
Y
Y
Ogryzko
V V
VV
Howard
B H
BH
Kedes
L
L
Wang
J Y
JY
Graessmann
A
A
Nakatani
Y
Y
Levrero
M
M
D000102:Acetyl-CoA C-Acyltransferase / Q000378:metabolism*; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000494:pharmacology; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D050881:E1A-Associated p300 Protein; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D051548:Histone Acetyltransferases; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D017570:MyoD Protein / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism / Q000494:pharmacology; D012319:RNA Polymerase II / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology; D015533:Transcriptional Activation / Q000502:physiology; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000102:Acetyl-CoA C-Acyltransferase; D000123:Acetyltransferases; D000957:Antigens, Viral, Tumor; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D050881:E1A-Associated p300 Protein; D051548:Histone Acetyltransferases; D009097:Multienzyme Complexes; D017570:MyoD Protein; D009687:Nuclear Proteins; D012319:RNA Polymerase II; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494364:Crebbp protein, mouse; C494361:Ep300 protein, mouse