Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Dev Cell. 2013 May 28;25(4):417-26. doi: 10.1016/j.devcel.2013.04.017.
Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, the 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 2,584 genes, of which 81% were differentially expressed between atria and ventricles, suggesting that a major function of myocardial COUP-TFII is to determine 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 atrial identity through direct binding and by modulating expression of a broad spectrum of genes that have an impact on atrial development and function.
心房和心室表现出明显的分子特征，这些特征导致了两个心脏腔室在结构和功能上的差异。然而，决定这些差异的因素在很大程度上还没有被定义。心肌细胞特异性 COUP-TFII 缺失会导致心室化的心房表现出类似心室的动作电位、心肌细胞大小增加以及广泛的 T 管形成。心房特征的变化伴随着 2584 个基因的改变，其中 81%在心房和心室之间存在差异表达，这表明心肌细胞 COUP-TFII 的一个主要功能是决定心房的特征。使用 E13.5 心房进行的染色质免疫沉淀分析鉴定了经典的心房-心室特征基因 Tbx5、Hey2、Irx4、MLC2v、MLC2a 和 MLC1a 以及许多其他心脏基因作为潜在的 COUP-TFII 直接靶标。总之，我们的结果表明，COUP-TFII 通过直接结合和调节广泛影响心房发育和功能的基因表达来赋予心房特征。
