Small Eric M, Warkman Andrew S, Wang Da-Zhi, Sutherland Lillian B, Olson Eric N, Krieg Paul A
Department of Cell Biology and Anatomy, University of Arizona Health Sciences Center, 1501 N. Campbell Avenue, PO Box 245044, Tucson, AZ 85724, USA.
Development. 2005 Mar;132(5):987-97. doi: 10.1242/dev.01684. Epub 2005 Jan 26.
Myocardin is a cardiac- and smooth muscle-specific cofactor for the ubiquitous transcription factor serum response factor (SRF). Using gain-of-function approaches in the Xenopus embryo, we show that myocardin is sufficient to activate transcription of a wide range of cardiac and smooth muscle differentiation markers in non-muscle cell types. We also demonstrate that, for the myosin light chain 2 gene (MLC2), myocardin cooperates with the zinc-finger transcription factor Gata4 to activate expression. Inhibition of myocardin activity in Xenopus embryos using morpholino knockdown methods results in inhibition of cardiac development and the absence of expression of cardiac differentiation markers and severe disruption of cardiac morphological processes. We conclude that myocardin is an essential component of the regulatory pathway for myocardial differentiation.
心肌素是普遍存在的转录因子血清反应因子(SRF)的心脏和平滑肌特异性辅因子。利用非洲爪蟾胚胎中的功能获得方法,我们发现心肌素足以激活非肌肉细胞类型中多种心脏和平滑肌分化标志物的转录。我们还证明,对于肌球蛋白轻链2基因(MLC2),心肌素与锌指转录因子Gata4协同激活表达。使用吗啉代敲低方法抑制非洲爪蟾胚胎中的心肌素活性会导致心脏发育受到抑制,心脏分化标志物表达缺失以及心脏形态学过程严重紊乱。我们得出结论,心肌素是心肌分化调控途径的重要组成部分。