Abstract
The molecular mechanism(s) that are responsible for suppressing MyoD's transcriptional activities in undifferentiated skeletal muscle cells have not yet been determined. We now show that MyoD associates with a histone deacetylase-1 (HDAC1) in these cells and that this interaction is responsible for silencing MyoD-dependent transcription of endogenous p21 as well as muscle-specific genes. Specifically, we present evidence that HDAC1 can bind directly to MyoD and use an acetylated MyoD as a substrate in vitro, whereas a mutant version of HDAC1 (H141A) can not. Further more, this mutant also fails to repress MyoD-mediated transcription in vivo, and unlike wild-type HDAC1 it can not inhibit myogenic conversion, as judged by confocal microscopy. Finally, we show that an endogenous MyoD can be acetylated upon its conversion to a hypophosphorylated state and only when the cells have been induced to differentiate. These results provide for a model which postulates that MyoD may be co-dependent on HDAC1 and P/CAF for temporally controlling its transcriptional activity before and after the differentiation of muscle cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylation
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Acetyltransferases / genetics
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Acetyltransferases / metabolism
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Animals
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cell Differentiation
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Cell Line
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Cell Line, Transformed
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics
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Histone Acetyltransferases
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Histone Deacetylase 1
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism
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Histone Deacetylases / physiology*
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Humans
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Jurkat Cells
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Mice
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Muscle, Skeletal / cytology
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Muscle, Skeletal / physiology*
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MyoD Protein / genetics
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MyoD Protein / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Promoter Regions, Genetic
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors
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Transcription, Genetic*
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p300-CBP Transcription Factors
Substances
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CDKN1A protein, human
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Cdkn1a protein, mouse
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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MyoD Protein
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Nuclear Proteins
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Trans-Activators
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Transcription Factors
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Acetyltransferases
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Histone Acetyltransferases
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p300-CBP Transcription Factors
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p300-CBP-associated factor
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HDAC1 protein, human
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Histone Deacetylase 1
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Histone Deacetylases