Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetyltransferases / metabolism*
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Animals
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Blotting, Western
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Cell Differentiation
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Cell Line
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Chromatin / metabolism
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / metabolism
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Dose-Response Relationship, Drug
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E1A-Associated p300 Protein
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Genes, Dominant
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Genes, Reporter
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Histone Acetyltransferases
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Immunohistochemistry
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Mice
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Microscopy, Fluorescence
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Muscles / physiology*
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Mutation
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Myogenin / metabolism
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Nuclear Proteins / metabolism*
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Precipitin Tests
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Promoter Regions, Genetic
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Recombinant Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Saccharomyces cerevisiae Proteins*
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Time Factors
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Trans-Activators / metabolism*
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Transcription, Genetic
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Transcriptional Activation
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Transfection
Substances
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Cdkn1a protein, mouse
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Chromatin
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Myog protein, mouse
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Myogenin
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Nuclear Proteins
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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Acetyltransferases
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E1A-Associated p300 Protein
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Ep300 protein, mouse
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Histone Acetyltransferases