title: Myocardin is a master regulator of smooth muscle gene expression.
abstract: Virtually all smooth muscle genes analyzed to date contain two or more essential binding sites for serum response factor (SRF) in their control regions. Because SRF is expressed in a wide range of cell types, it alone cannot account for smooth muscle-specific gene expression. We show that myocardin, a cardiac muscle- and smooth muscle-specific transcriptional coactivator of SRF, can activate smooth muscle gene expression in a variety of nonmuscle cell types via its association with SRF. Homodimerization of myocardin is required for maximal transcriptional activity and provides a mechanism for cooperative activation of smooth muscle genes by SRF-myocardin complexes bound to different SRF binding sites. These findings identify myocardin as a master regulator of smooth muscle gene expression and explain how SRF conveys smooth muscle specificity to its target genes.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Wang
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Wang
authors.forename: G C Teg
authors.initials: GC
authors.lastname: Pipes
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D019281:Dimerization; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009130:Muscle, Smooth / Q000254:growth & development / Q000378:metabolism*; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D026362:Serum Response Factor / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000099251:Myocardin
chemical_list: D009687:Nuclear Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D000099251:Myocardin