BRG1 promotes COUP-TFII expression and venous specification during embryonic vascular development
BRG1 promotes COUP-TFII expression and venous specification during embryonic vascular development
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DOI：
10.1242/dev.087379
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发表时间：
2013-03-01
期刊：
影响因子：
4.6
通讯作者：
Griffin, Courtney T.
中科院分区：
文献类型：
--
作者：
Davis, Reema B.;Curtis, Carol D.;Griffin, Courtney T.
动脉和静脉在胚胎血液循环开始之前获得不同的分子身份，并且它们的特化对于血管发育至关重要。转录因子COUP-TFII目前在控制静脉命运的信号通路的顶部起作用。它通过抑制Notch信号传导和随后的内皮细胞动脉化来促进静脉身份，但对静脉中COUP-TFII表达的调控机制一无所知。我们现在报告，染色质重塑酶BRG 1促进小鼠胚胎发育过程中静脉内皮细胞COUP-TFII的表达。从血管内皮细胞中有条件地删除Brg 1导致COUP-TFII表达下调和静脉上动脉标记物的异常表达。BRG 1通过结合COUP-TFII启动子内的保守调控元件并重塑染色质以使启动子可接近转录机器来促进COUP-TFII表达。这项研究提供了第一次描述的一个因素，促进COUP-TFII表达血管内皮细胞，并强调了一个新的作用，染色质重塑静脉规格。
Arteries and veins acquire distinct molecular identities prior to the onset of embryonic blood circulation, and their specification is crucial for vascular development. The transcription factor COUP-TFII currently functions at the top of a signaling pathway governing venous fate. It promotes venous identity by inhibiting Notch signaling and subsequent arterialization of endothelial cells, yet nothing is known about what regulates COUP-TFII expression in veins. We now report that the chromatin-remodeling enzyme BRG1 promotes COUP-TFII expression in venous endothelial cells during murine embryonic development. Conditional deletion of Brg1 from vascular endothelial cells resulted in downregulated COUP-TFII expression and aberrant expression of arterial markers on veins. BRG1 promotes COUP-TFII expression by binding conserved regulatory elements within the COUP-TFII promoter and remodeling chromatin to make the promoter accessible to transcriptional machinery. This study provides the first description of a factor promoting COUP-TFII expression in vascular endothelium and highlights a novel role for chromatin remodeling in venous specification.