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

Proc Natl Acad Sci U S A. 2007 May 8;104(19):7975-80. doi: 10.1073/pnas.0702447104. Epub 2007 Apr 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Female
  • Gene Expression Regulation*
  • Heart / embryology
  • Heart Atria / metabolism*
  • Heart Septal Defects, Ventricular / etiology
  • Mice
  • Myocardial Contraction*
  • Rats
  • Receptors, Notch / physiology
  • Repressor Proteins / physiology*
  • Signal Transduction
  • T-Box Domain Proteins / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • Hey2 protein, mouse
  • Receptors, Notch
  • Repressor Proteins
  • T-Box Domain Proteins
  • T-box transcription factor 5
  • Atrial Natriuretic Factor