Wang Zhigao, Wang Da-Zhi, Pipes G C Teg, Olson Eric N
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7129-34. doi: 10.1073/pnas.1232341100. Epub 2003 May 19.
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.
迄今为止，几乎所有已分析的平滑肌基因在其调控区域都含有两个或更多个血清反应因子（SRF）的必需结合位点。由于SRF在多种细胞类型中都有表达，因此仅靠它自身并不能解释平滑肌特异性基因的表达。我们发现，心肌素是一种心肌和平滑肌特异性的SRF转录共激活因子，它可以通过与SRF结合，在多种非肌肉细胞类型中激活平滑肌基因的表达。心肌素的同源二聚化对于最大转录活性是必需的，并为与不同SRF结合位点结合的SRF-心肌素复合物协同激活平滑肌基因提供了一种机制。这些发现确定心肌素是平滑肌基因表达的主要调节因子，并解释了SRF如何将平滑肌特异性传递给其靶基因。
