Abstract
Skeletal muscle differentiation has been shown to be dependent on the expression of Rb and p300. We recently cloned a novel inhibitor of muscle differentiation called EID-1, which interacted with both of these factors. In a database search for related molecules, we have cloned and characterized a new EID-1 family member, EID-2. This 28-kDa protein encodes a 236-amino-acid protein with significant similarity to EID-1 in its C-terminus. EID-2 displays developmentally regulated expression with high levels in adult heart and brain. Overexpression of EID-2 inhibits muscle-specific gene expression through inhibition of MyoD-dependent transcription. This inhibitory effect on gene expression can be explained by EID-2's ability to associate with and inhibit the acetyltransferase activity of p300. These data suggest that EID-1 and -2 represent a novel family of proteins that negatively regulate differentiation through a p300-dependent mechanism.
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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Acetyltransferases / metabolism
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Actins / genetics
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Actins / metabolism
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Adult
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Amino Acid Sequence
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Animals
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Base Sequence
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Cell Line
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Cell Line, Tumor
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Cells, Cultured
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Cloning, Molecular
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DNA, Complementary / chemistry
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DNA, Complementary / genetics
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Female
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Gene Expression
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Histone Acetyltransferases
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Humans
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Inhibitor of Differentiation Protein 2
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Intracellular Signaling Peptides and Proteins*
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Molecular Sequence Data
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Molecular Weight
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Muscle, Skeletal / cytology
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Muscle, Skeletal / metabolism
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MyoD Protein / genetics
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MyoD Protein / metabolism*
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Myosin Heavy Chains / genetics
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Myosin Heavy Chains / metabolism
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism*
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Protein Binding
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Sequence Alignment
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Sequence Analysis, DNA
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Sequence Homology, Amino Acid
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription, Genetic
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Transcriptional Activation
Substances
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Actins
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Carrier Proteins
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DNA, Complementary
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EID-2 protein, mouse
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EID2 protein, human
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Inhibitor of Differentiation Protein 2
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Intracellular Signaling Peptides and Proteins
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MyoD Protein
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Nuclear Proteins
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Trans-Activators
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Acetyltransferases
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Histone Acetyltransferases
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Myosin Heavy Chains
Associated data
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GENBANK/AY251272
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GENBANK/AY251273