Abstract 15245: COUP-TFII Determines the Atrial Identity Through Regulation of Multiple Pathways
Emerging evidence reveals the presence of plasticity in cardiomyocytes that allows them to be reprogrammed into atrial, ventricular or nodal fates. We show that Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII), a transcription factor that is restrictively expressed in the atria, serves as a major regulator to determine the atrial identity in differentiating cardiomyocytes in vivo. Cardiomyocyte-specific ablation of COUP-TFII produces ventricle-like cardiomyocytes in the working myocardium of the atrial compartment. Results from immunohistochemistry, gene expression profiling and chromatin immunoprecipitation analyses indicate that COUP-TFII promotes atrial and suppresses ventricular and cardiac conduction system gene expression via direct and indirect mechanisms. In the embryonic atria, COUP-TFII directly controls the expression of Tbx5, Hey2, Irx4, CaMKII kinases, MEF2 transcription factors and many other atrial/ventricular genes. Furthermore, preliminary analyses also show a direct suppression of gene expression by COUP-TFII on nodal genes, including Tbx3 and Id2. Taking together, our results demonstrate that COUP-TFII confers atrial identity by regulating multiple pathways in differentiating cardiomyocytes to promote atrial fate, while preventing acquisition of ventricular and nodal characteristics.
- © 2013 by American Heart Association, Inc.