An arterial-specific enhancer of the human endothelin converting enzyme 1 (ECE1) gene is synergistically activated by Sox17, FoxC2, and Etv2.
An arterial-specific enhancer of the human endothelin converting enzyme 1 (ECE1) gene is synergistically activated by Sox17, FoxC2, and Etv2.
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DOI：
10.1016/j.ydbio.2014.08.027
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发表时间：
2014-11-15
影响因子：
2.7
通讯作者：
Black, Brian L.
中科院分区：
文献类型：
--
作者：
Robinson, Ashley S.;Materna, Stefan C.;Barnes, Ralston M.;De Val, Sarah;Xu, Shan-Mei;Black, Brian L.
内皮素转换酶-1（Ece-1）是内皮素信号通路的重要组成部分，是胚胎发育所必需的，并且是血管张力的重要调节剂，然而ECE 1基因的转录调节在很大程度上仍然未知。在这里，我们定义的活性和调节的增强子从人ECE 1基因座在体内。在此鉴定的增强子在内皮祖细胞的初始规格后不久就变得活跃，并且依赖于保守的FOX：ETS基序（Forkhead转录因子和Ets转录因子Etv 2的复合结合位点）的体内活性。ECE 1 FOX：ETS基序被FoxC 2和Etv 2结合并协同激活，但与其他描述的FOX：ETS依赖性增强子不同，在转基因小鼠胚胎中，ECE 1增强子活性在胚胎第9.5天被限制在动脉内皮和内皮细胞。ECE 1内皮增强子还含有一个进化上保守的共有SOX结合位点，这是转基因小鼠胚胎中活性所必需的。重要的是，ECE 1 SOX位点被Sox 17结合和激活，Sox 17是一种参与内皮细胞分化的转录因子，也是动脉身份的重要调节因子。此外，ECE 1增强子通过FoxC 2、Etv 2和Sox 17的组合作用协同激活。虽然Sox 17是动脉身份所必需的，但在内皮细胞中很少发现直接的转录靶点。因此，这项工作有重要的意义，我们的理解内皮细胞的规格和动脉亚规格。
Endothelin-converting enzyme-1 (Ece-1), a crucial component of the Endothelin signaling pathway, is required for embryonic development and is an important regulator of vascular tone, yet the transcriptional regulation of the ECE1 gene has remained largely unknown. Here, we define the activity and regulation of an enhancer from the human ECE1 locus in vivo. The enhancer identified here becomes active in endothelial progenitor cells shortly after their initial specification and is dependent on a conserved FOX:ETS motif, a composite binding site for Forkhead transcription factors and the Ets transcription factor Etv2, for activity in vivo. The ECE1 FOX:ETS motif is bound and cooperatively activated by FoxC2 and Etv2, but unlike other described FOX:ETS-dependent enhancers, ECE1 enhancer activity becomes restricted to arterial endothelium and endocardium by embryonic day 9.5 in transgenic mouse embryos. The ECE1 endothelial enhancer also contains an evolutionarily-conserved, consensus SOX binding site, which is required for activity in transgenic mouse embryos. Importantly, the ECE1 SOX site is bound and activated by Sox17, a transcription factor involved in endothelial cell differentiation and an important regulator of arterial identity. Moreover, the ECE1 enhancer is cooperatively activated by the combinatorial action of FoxC2, Etv2, and Sox17. Although Sox17 is required for arterial identity, few direct transcriptional targets have been identified in endothelial cells. Thus, this work has important implications for our understanding of endothelial specification and arterial subspecification.
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影响因子：
14.9
作者：
HOSKING, BM;MUSCAT, GEO;DUNN, TL
通讯作者：
DUNN, TL
影响因子：
5.3
作者：
Anderson, JP;Dodou, E;Black, BL
通讯作者：
Black, BL
影响因子：
3.5
作者：
Funke-Kaiser, H;Bolbrinker, J;Orzechowski, HD
通讯作者：
Orzechowski, HD
DOI：
10.1111/j.1432-1033.1997.00520.x
发表时间：
1997-03-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Kido, T;Sawamura, T;Masaki, T
通讯作者：
Masaki, T
Sox17 在小鼠胚胎发生过程中的双谱系特异性表达。
影响因子：
5.2
作者：
Choi, Eunyoung;Kraus, Marine R-C.;Lemaire, Laurence A.;Yoshimoto, Momoko;Vemula, Sasidhar;Potter, Leah A.;Manduchi, Elisabetta;Stoeckert, Christian J., Jr.;Grapin-Botton, Anne;Magnuson, Mark A.
通讯作者：
Magnuson, Mark A.