Essential roles of the bHLH transcription factor Hrt2 in repression of atrial gene expression and maintenance of postnatal cardiac function

Mei Xin, Eric M. Small, Eva Van Rooij, Xiaoxia Qi, James A. Richardson, Deepak Srivastava, Osamu Nakagawa, Eric N. Olson

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7975-7980
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number19
DOIs
StatePublished - May 8 2007

Keywords

  • Congenital heart disease
  • Heart development
  • Heart failure

ASJC Scopus subject areas

  • General

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