Oh Jiyeon, Wang Zhigao, Wang Da-Zhi, Lien Ching-Ling, Xing Weibing, Olson Eric N
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9148, USA.
Mol Cell Biol. 2004 Oct;24(19):8519-28. doi: 10.1128/MCB.24.19.8519-8528.2004.
Myocardin is a transcriptional coactivator that regulates cardiac and smooth muscle gene expression by associating with serum response factor. We show that GATA transcription factors can either stimulate or suppress the transcriptional activity of myocardin, depending on the target gene. Modulation of myocardin activity by GATA4 is mediated by the physical interaction of myocardin with the DNA binding domain of GATA4 but does not require binding of GATA4 to DNA. Paradoxically, the transcription activation domain of GATA4 is dispensable for the stimulatory effect of GATA4 on myocardin activity but is required for repression of myocardin activity. The ability of GATA transcription factors to modulate myocardin activity provides a potential mechanism for fine tuning the expression of serum response factor target genes in a gene-specific manner.
心肌素是一种转录共激活因子，它通过与血清反应因子结合来调节心脏和平滑肌基因的表达。我们发现，GATA转录因子可根据靶基因的不同，对心肌素的转录活性产生刺激或抑制作用。GATA4对心肌素活性的调节是通过心肌素与GATA4的DNA结合结构域的物理相互作用介导的，但并不需要GATA4与DNA结合。矛盾的是，GATA4的转录激活结构域对于GATA4对心肌素活性的刺激作用并非必需，但对于心肌素活性的抑制却是必需的。GATA转录因子调节心肌素活性的能力为以基因特异性方式微调血清反应因子靶基因的表达提供了一种潜在机制。
