Literature DB >> 17173866

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

Shinobu Kuratomi1, Akiko Kuratomi, Koichiro Kuwahara, Takahiro M Ishii, Kazuwa Nakao, Yoshihiko Saito, Makoto Takano.   

Abstract

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.

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Year:  2006        PMID: 17173866     DOI: 10.1016/j.bbrc.2006.11.119

Source DB:  PubMed          Journal:  Biochem Biophys Res Commun        ISSN: 0006-291X            Impact factor:   3.575


  11 in total

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