Project description: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.
Project description:Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, 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. We used microarrays to examine the molecular profile of cardiomyocyte-specific COUP-TFII knockout adult atria in comparison with that of normal atria. We extracted RNA from mutant right atria, control right atria and control ventricles from 2 months old adult mice, followed by gene expression profiling using Affymetrix microarrays.
Project description:Atria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, 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. We used microarrays to examine the molecular profile of cardiomyocyte-specific COUP-TFII knockout adult atria in comparison with that of normal atria.
Project description:Embryonic cardiomyocytes possess the plasticity to choose between atrial and ventricular fates. For a limited window of time, the transcription factor COUP-TFII (Nr2f2) sufficiently and essentially confers the atrial identity through direct and indirect regulation of nearly half of chamber specific genes. Examination of COUP-TFII binding sites in embryonic artia
Project description:Embryonic cardiomyocytes possess the plasticity to choose between atrial and ventricular fates. For a limited window of time, the transcription factor COUP-TFII (Nr2f2) sufficiently and essentially confers the atrial identity through direct and indirect regulation of nearly half of chamber specific genes.