CBP/p300 and muscle differentiation: no HAT, no muscle.
Terminal differentiation of muscle cells follows a precisely orchestrated program of transcriptional regulatory events at the promoters of both muscle-specific and ubiquitous genes. Two distinct families of transcriptional co-activators, GCN5/PCAF and CREB-binding protein (CBP)/p300, are crucial to this process. While both possess histone acetyl-transferase (HAT) activity, previous studies have failed to identify a requirement for CBP/p300 HAT function in myogenic differentiation. We have addressed this issue directly using a chemical inhibitor of CBP/p300 in addition to a negative transdominant mutant. Our results clearly demonstrate that CBP/p300 HAT activity is critical for myogenic terminal differentiation. Furthermore, this requirement is restricted to a subset of events in the differentiation program: cell fusion and specific gene expression. These data help to define the requirements for enzymatic function of distinct coactivators at different stages of the muscle cell differentiation program.
Polesskaya
A
A
CNRS UPR 9079 and Service de Cytofluorométrie, Institut André Lwoff, 7 rue Guy Moquet, 94800 Villejuif, France.
Naguibneva
I
I
Fritsch
L
L
Duquet
A
A
Ait-Si-Ali
S
S
Robin
P
P
Vervisch
A
A
Pritchard
L L
LL
Cole
P
P
Harel-Bellan
A
A
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D050881:E1A-Associated p300 Protein; D005799:Genes, Dominant; D017930:Genes, Reporter; D051548:Histone Acetyltransferases; D007150:Immunohistochemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000502:physiology*; D009154:Mutation; D018008:Myogenin / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
C493957:Cdkn1a protein, mouse; D002843:Chromatin; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C503801:Myog protein, mouse; D018008:Myogenin; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D000123:Acetyltransferases; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D051548:Histone Acetyltransferases