The cardiac homeobox transcription factor Nkx2-5 is a major determinant of cardiac identity and cardiac morphogenesis. Nkx2-5 operates as part of a complex and mutually reinforcing network of early transcription factors of the homeobox, GATA zinc finger and MADS domain families to initiate the program of cardiac development and differentiation, particularly in outflow tract precursor cells in the second heart field (SHF). We have now found evidence for another aspect of cardiac transcription factor cooperativity between Nkx2-5 and the cardiac enriched MADS domain transcription factor Srf. Specifically, Srf interaction with an evolutionarily conserved binding site in the Nkx2-5 CpG island-like proximal promoter is required for cardiac specific expression mediated by an SHF enhancer, and for combinatorial activation of these elements by cardiac transcription factors. These results provide further insight into cooperative gene regulation during cardiogenesis at the level of promoter-enhancer interactions.

中文翻译：

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Nkx2-5 的第二心脏场特异性表达需要启动子与 Srf 的近端相互作用

心脏同源盒转录因子 Nkx2-5 是心脏特性和心脏形态发生的主要决定因素。Nkx2-5 作为同源框、GATA 锌指和 MADS 域家族早期转录因子复杂且相互增强的网络的一部分运作，以启动心脏发育和分化程序，特别是在第二心脏区域的流出道前体细胞中。 SHF)。我们现在已经找到了 Nkx2-5 和心脏富集的 MADS 域转录因子 Srf 之间心脏转录因子协同作用的另一个方面的证据。具体来说，Srf 与 Nkx2-5 CpG 岛样近端启动子中进化上保守的结合位点的相互作用是由 SHF 增强子介导的心脏特异性表达所必需的，以及通过心脏转录因子组合激活这些元件。这些结果提供了在启动子-增强子相互作用水平上心脏发生过程中协同基因调控的进一步见解。