Atrial Identity Is Determined by a COUP-TFII Regulatory Network

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

来源：Developmental Cell, 2013, 25(4): 417-426.

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.

• 出版日期2013-5-28