title: NRSF regulates the developmental and hypertrophic changes of HCN4 transcription in rat cardiac myocytes.
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.
authors.affiliation: Department of Physiology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kuratomi
authors.forename: Akiko
authors.initials: A
authors.lastname: Kuratomi
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kuwahara
authors.forename: Takahiro M
authors.initials: TM
authors.lastname: Ishii
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
authors.forename: Makoto
authors.initials: M
authors.lastname: Takano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000196:embryology* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D032383:Myocytes, Cardiac / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D000099229:RE1-Silencing Transcription Factor
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C513836:HCN4 protein, rat