Target gene-specific modulation of myocardin activity by GATA transcription factors
Target gene-specific modulation of myocardin activity by GATA transcription factors
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DOI：
10.1128/mcb.24.19.8519-8528.2004
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发表时间：
2004-10-01
影响因子：
5.3
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Oh, J;Wang, ZG;Olson, EN
Myocardin是一种转录辅助激活因子，通过与血清反应因子结合来调节心肌和平滑肌基因的表达。我们发现，GATA转录因子可以刺激或抑制myocardin的转录活性，这取决于目标基因。GATA4对Myocardin活性的调节是通过Myocardin与GATA4的DNA结合域的物理相互作用来实现的，但不需要GATA4与DNA结合。矛盾的是，GATA4的转录激活结构域对于GATA4刺激肌钙蛋白活性的作用是不必要的，但对于抑制肌钙蛋白活性是必需的。GATA转录因子调节肌钙蛋白活性的能力为以基因特异的方式微调血清反应因子靶基因的表达提供了潜在的机制。
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.