Essential roles of the bHLH transcription factor Hrt2 in repression of atrial gene expression and maintenance of postnatal cardiac function
- 8 May 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 104 (19), 7975-7980
- https://doi.org/10.1073/pnas.0702447104
Abstract
The basic helix-loop-helix transcriptional repressor Hairy-related transcription factor 2 (Hrt2) is expressed in ventricular, but not atrial, cardiomyocytes, and in endothelial and vascular smooth muscle cells. Mice homozygous for a null mutation of Hrt2 die perinatally from a spectrum of cardiac abnormalities, raising questions about the specific functions of this transcriptional regulator in individual cardiac cell lineages. Using a conditional Hrt2 null allele, we show that cardiomyocyte-specific deletion of Hrt2 in mice results in ectopic activation of atrial genes in ventricular myocardium with an associated impairment of cardiac contractility and a unique distortion in morphology of the right ventricular chamber. Consistent with the atrialization of ventricular gene expression in Hrt2 mutant mice, forced expression of Hrt2 in atrial cardiomyocytes is sufficient to repress atrial cardiac genes. These findings reveal a ventricular myocardial cell-autonomous function for Hrt2 in the suppression of atrial cell identity and the maintenance of postnatal cardiac function.Keywords
This publication has 54 references indexed in Scilit:
- CHF1/Hey2 Plays a Pivotal Role in Left Ventricular Maturation Through Suppression of Ectopic Atrial Gene ExpressionCirculation Research, 2007
- Hrt and Hes negatively regulate Notch signaling through interactions with RBP-JκBiochemical and Biophysical Research Communications, 2006
- Targeted Overexpression of Sarcolipin in the Mouse Heart Decreases Sarcoplasmic Reticulum Calcium Transport and Cardiac ContractilityPublished by Elsevier BV ,2006
- Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch signaling in the developing cardiovascular systemDevelopmental Biology, 2004
- Down-regulation of sarcolipin mRNA expression in chronic atrial fibrillationEuropean Journal of Clinical Investigation, 2004
- Bidirectional Modulation of Cystine/Glutamate Exchanger Activity in Cultured Cortical AstrocytesAnnals of the New York Academy of Sciences, 2003
- Patterning the vertebrate heartNature Reviews Genetics, 2002
- Tie2-Cre Transgenic Mice: A New Model for Endothelial Cell-Lineage Analysis in VivoDevelopmental Biology, 2001
- Comparative Analysis of the Human and Mouse Hey1 Promoter: Hey Genes Are New Notch Target GenesBiochemical and Biophysical Research Communications, 2000
- Identification and Expression of a Novel Family of bHLH cDNAs Related to Drosophila Hairy and Enhancer of SplitBiochemical and Biophysical Research Communications, 1999