Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators
Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators
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DOI：
10.1128/mcb.20.20.7550-7558.2000
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发表时间：
2000-10-01
影响因子：
5.3
通讯作者：
Schwartz, RJ
中科院分区：
文献类型：
--
作者：
Belaguli, NS;Sepulveda, JL;Schwartz, RJ
心脏组织限制性富集转录因子之间的组合相互作用可能促进心脏组织限制性基因的表达。在这里，我们表明，MADS盒因子血清反应因子（SRF）与锌指蛋白加塔-4协同激活许多肌源性和非肌源性血清反应元件（SRE）依赖的启动子在CV1成纤维细胞，在加塔结合位点的情况下，协同激活依赖于结合的SRF在心脏和骨骼α-肌动蛋白启动子的近端CArG盒序列。加塔-4的C-末端激活结构域对于与SRF的协同共激活是必须的，并且其N-末端结构域和第一锌指是抑制性的。SRF和加塔-4通过其MADS盒和第二锌指结构域在体内和体外物理结合，如通过蛋白A拉出测定和通过使用Gal 4融合蛋白的体内单杂交转染测定所确定的。其他心血管组织限制性加塔因子，如加塔-5和加塔-6在共激活SRE依赖性靶点方面与加塔-4相当。因此，MADS盒和C4锌指蛋白之间的相互作用，一种新的调节模式，介导SRE依赖的基因表达的激活。
Combinatorial interaction among cardiac tissue-restricted enriched transcription factors may facilitate the expression of cardiac tissue-restricted genes. Here we show that the MADS box factor serum response factor (SRF) cooperates with the zinc finger protein GATA-4 to synergistically activate numerous myogenic and nonmyogenic serum response element (SRE)-dependent promoters in CV1 fibroblasts, In the absence of GATA binding sites, synergistic activation depends on binding of SRF to the proximal CArG box sequence in the cardiac and skeletal alpha-actin promoter. GATA-4's C-terminal activation domain is obligatory for synergistic coactivation with SRF, and its N-terminal domain and first zinc finger are inhibitory. SRF and GATA-4 physically associate both in vivo and in vitro through their MADS box and the second zinc finger domains as determined by protein A pullout assays and by in vivo one-hybrid transfection assays using Gal4 fusion proteins. Other cardiovascular tissue-restricted GATA factors, such as GATA-5 and GATA-6 were equivalent to GATA-4 in coactivating SRE-dependent targets. Thus, interaction between the MADS box and C4 zinc finger proteins, a novel regulatory paradigm, mediates activation of SRE-dependent gene expression.