Atrial identity is determined by a COUP-TFII regulatory network.
Atrial identity is determined by a COUP-TFII regulatory network.
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DOI：
10.1016/j.devcel.2013.04.017
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发表时间：
2013-05-28
影响因子：
11.8
通讯作者：
Tsai, Sophia Y.
中科院分区：
文献类型：
--
作者：
Wu, San-pin;Cheng, Chiang-Min;Lanz, Rainer B.;Wang, Tiannan;Respress, Jonathan L.;Ather, Sameer;Chen, Wen;Tsai, Shaw-Jenq;Wehrens, Xander H. T.;Tsai, Ming-Jer;Tsai, Sophia Y.
心房和心室表现出不同的分子谱，这在两个心脏隔室之间产生结构和功能差异。然而，决定这些差异的因素在很大程度上仍不明确。心肌细胞特异性COUP-TFII消融产生心室化心房，其表现出心室样动作电位、心肌细胞大小增加和广泛的T-小管发育。心房特征的改变伴随着2584个基因的改变，其中81%的基因在心房和心室之间差异表达，这表明心肌COUP-TFII的主要功能是确定心房的身份。使用E13.5心房的染色质免疫沉淀试验鉴定了经典的房室身份基因Tbx 5、Hey 2、Irx 4、MLC 2 v、MLC 2a和MLC 1a以及许多其他心脏基因，作为潜在的COUP-TFII直接靶点。总的来说，我们的研究结果表明，COUP-TFII通过直接结合和调节对心房发育和功能有影响的广谱基因的表达来赋予心房身份。
Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP-TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T-tubules. Changes in atrial characteristics are accompanied by alterations of 2584 genes, in which 81% of them were differentially expressed between atria and ventricles, suggesting that a major function of myocardial COUP-TFII is to determine the atrial identity. Chromatin immunoprecipitation assays using E13.5 atria identified classic atrial-ventricular identity genes Tbx5, Hey2, Irx4, MLC2v, MLC2a and MLC1a, among many other cardiac genes, as potential COUP-TFII direct targets. Collectively, our results reveal that COUP-TFII confers the atrial identity through direct binding and modulating expression of a broad spectrum of genes that have an impact on atrial development and function.
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