Atrial identity is determined by a COUP-TFII regulatory network.
Dev Cell, 2013/5/28;25(4):417-26.
Wu SP[1], Cheng CM, Lanz RB, Wang T, Respress JL, Ather S, Chen W, Tsai SJ, Wehrens XH, Tsai MJ, Tsai SY
Affiliations
PMID: 23725765
Impact factor: 13.417
Abstract
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.
MeSH terms
Action Potentials; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Cell Proliferation; Cell Size; Chromatin Immunoprecipitation; Embryo, Mammalian; Gene Expression Regulation, Developmental; Heart Atria; Heart Ventricles; Homeodomain Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Myocytes, Cardiac; Protein Binding; RNA, Messenger; Repressor Proteins; T-Box Domain Proteins; Tumor Suppressor Proteins
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