Second heart field-specific expression of Nkx2-5 requires promoter proximal interaction with Srf.

Second heart field-specific expression of Nkx2-5 requires promoter proximal interaction with Srf.
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DOI:
10.1016/j.mod.2020.103615
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发表时间:
2020-06
影响因子:
2.6
通讯作者:
Lee KH
Lee KH
中科院分区:
生物学4区
文献类型:
--
作者:
Clark CD;Lee KH

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心脏同源框转录因子Nkx 2 -5是心脏特性和心脏形态发生的主要决定因素。Nkx 2 -5作为同源异型盒、加塔锌指和MADS结构域家族的早期转录因子的复杂且相互增强的网络的一部分起作用,以启动心脏发育和分化的程序,特别是在第二心脏区域(SHF)的流出道前体细胞中。我们现在已经发现了Nkx 2 -5和心脏富集MADS结构域转录因子Srf之间心脏转录因子协同性的另一个方面的证据。具体而言,Srf与Nkx 2 -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以及心脏转录因子对这些元件的组合激活所必需的。这些结果提供了进一步了解心脏发生过程中的启动子-增强子相互作用水平的协同基因调控。
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.
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