First Author | Wu SP | Year | 2013 |
Journal | Dev Cell | Volume | 25 |
Issue | 4 | Pages | 417-26 |
PubMed ID | 23725765 | Mgi Jnum | J:198651 |
Mgi Id | MGI:5498603 | Doi | 10.1016/j.devcel.2013.04.017 |
Citation | Wu SP, et al. (2013) Atrial identity is determined by a COUP-TFII regulatory network. Dev Cell 25(4):417-26 |
abstractText | 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. |