NRSF regulates the developmental and hypertrophic changes of HCN4 transcription in rat cardiac myocytes

Biochem Biophys Res Commun. 2007 Feb 2;353(1):67-73. doi: 10.1016/j.bbrc.2006.11.119. Epub 2006 Dec 4.


The HCN4 channel shows differential expression patterns during the embryonic development and hypertrophy of hearts. Briefly, HCN4 expression is maximally activated in embryonic hearts and quickly diminishes after birth. However, it is reactivated during cardiac hypertrophy. The sequence analysis of HCN4 gene revealed the presence of a conserved NRSE motif, which is known to bind the transcriptional factor neuron-restrictive silencing factor (NRSF). A promoter analysis of HCN4 with rat cardiac myocytes identified the region inducing a basal transcriptional activity. This region drove a high activity in embryonic myocytes, but not in neonatal myocytes treated with hypertrophic agents. After confirming that NRSF protein binds to the NRSE, HCN4 promoter activities modified by NRSE were evaluated. With wild-type NRSE, the promoter activity correlated well with the developmental and hypertrophic changes of HCN4 expression, whereas mutant NRSE constructs failed. We conclude that the NRSE-NRSF system was implicated in HCN4 expression in cardiac myocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cardiomegaly / embryology*
  • Cardiomegaly / metabolism*
  • Cell Proliferation
  • Cells, Cultured
  • Gene Expression Regulation, Developmental
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Myocytes, Cardiac / metabolism*
  • Potassium Channels / metabolism*
  • Rats
  • Rats, Wistar
  • Repressor Proteins / metabolism*
  • Transcription Factors / metabolism*
  • Transcriptional Activation*


  • HCN4 protein, rat
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Potassium Channels
  • RE1-silencing transcription factor
  • Repressor Proteins
  • Transcription Factors