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Dev Cell. 2013 May 28;25(4):417-26. doi: 10.1016/j.devcel.2013.04.017.

Atrial identity is determined by a COUP-TFII regulatory network.

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1
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

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.

PMID:
23725765
PMCID:
PMC3687546
DOI:
10.1016/j.devcel.2013.04.017
[Indexed for MEDLINE]
Free PMC Article

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