TY - JOUR
T1 - Atrial Identity Is Determined by a COUP-TFII Regulatory Network
AU - Wu, San pin
AU - Cheng, Chiang Min
AU - Lanz, Rainer B.
AU - Wang, Tiannan
AU - Respress, Jonathan L.
AU - Ather, Sameer
AU - Chen, Wen
AU - Tsai, Shaw Jenq
AU - Wehrens, Xander H.T.
AU - Tsai, Ming Jer
AU - Tsai, Sophia Y.
N1 - Funding Information:
The authors would like to thank Dr. A.J. Marian (University of Texas Health Science Center at Houston) for providing the Myh6-cre mice before the line was available from the Jackson Laboratory. We also thank W. Qian and X.F. Tong for excellent technical support and J.R. Hebert for editing. This work was supported by National Institutes of Health grants HL76448 (S.Y.T.), DK45641 (M.-J.T.), and DK62434 and DK59820 (S.Y.T. and M.-J.T.) and Diabetes Research Center grant P30 DK079638 for core laboratory services.
PY - 2013/5/28
Y1 - 2013/5/28
N2 - 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.
AB - 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.
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U2 - 10.1016/j.devcel.2013.04.017
DO - 10.1016/j.devcel.2013.04.017
M3 - Article
C2 - 23725765
AN - SCOPUS:84878367020
SN - 1534-5807
VL - 25
SP - 417
EP - 426
JO - Developmental Cell
JF - Developmental Cell
IS - 4
ER -