Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor

Serum response factor (SRF) regulates transcription of numerous muscle and growth factor-inducible genes. Because SRF is not muscle specific, It has b een postulated to activate muscle genes by recruiting myogenic accessory fa ctors. Using a bioinformatics-based screen for unknown cardiac-specific gen es, we identified a novel and highly potent transcription factor, named myo cardin, that is expressed in cardiac and smooth muscle cells. Myocardin bel ongs to the SAP domain family of nuclear proteins and activates cardiac mus cle promoters by associating with SRF. Expression of a dominant negative mu tant of myocardin in Xenopus embryos interferes with myocardial cell differ entiation. Myocardin is the founding member of a class of muscle transcript ion factors and provides a mechanism whereby SRF can convey myogenic activi ty to cardiac muscle genes.