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 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.
Wang
D
D
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Chang
P S
PS
Wang
Z
Z
Sutherland
L
L
Richardson
J A
JA
Small
E
E
Krieg
P A
PA
Olson
E N
EN
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000502:physiology; D004625:Embryo, Nonmammalian; D020224:Expressed Sequence Tags; D017930:Genes, Reporter / Q000235:genetics; D051379:Mice; D008845:Microinjections; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D026362:Serum Response Factor; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics; D000099251:Myocardin
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D000099251:Myocardin