Abstract
Serum response factor (SRF) regulates transcription of numerous muscle and growth factor-inducible genes. Because SRF is not muscle specific, it has been postulated to activate muscle genes by recruiting myogenic accessory factors. Using a bioinformatics-based screen for unknown cardiac-specific genes, we identified a novel and highly potent transcription factor, named myocardin, that is expressed in cardiac and smooth muscle cells. Myocardin belongs to the SAP domain family of nuclear proteins and activates cardiac muscle promoters by associating with SRF. Expression of a dominant negative mutant of myocardin in Xenopus embryos interferes with myocardial cell differentiation. Myocardin is the founding member of a class of muscle transcription factors and provides a mechanism whereby SRF can convey myogenic activity to cardiac muscle genes.
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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Amino Acid Sequence
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Animals
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COS Cells
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Computational Biology*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Embryo, Mammalian / physiology
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Embryo, Nonmammalian
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Expressed Sequence Tags
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Genes, Reporter / genetics
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Mice
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Microinjections
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Molecular Sequence Data
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Muscle, Smooth / physiology
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Myocardium / metabolism*
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Promoter Regions, Genetic / genetics
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Protein Binding
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Sequence Alignment
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Serum Response Factor
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcriptional Activation / genetics*
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Xenopus laevis / embryology
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Xenopus laevis / genetics
Substances
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DNA-Binding Proteins
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Nuclear Proteins
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Recombinant Fusion Proteins
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Serum Response Factor
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Trans-Activators
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myocardin