title: Regulatory role of neuron-restrictive silencing factor in expression of TRPC1.
abstract: Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca(2+) channel (SOCC)-mediated Ca(2+) entry. Transfection of TRPC1 into primary cardiomyocytes increased NFAT activity, indicating a major role for TRPC1 in NFAT activation. Our findings strongly suggest that NRSF regulates TRP1 gene expression and causes changes in the levels of calcium entry through SOCCs.
authors.affiliation: Second Department of Internal Medicine, Akita University School of Medicine, Akita, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohba
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyoshi
authors.forename: Shinnsuke
authors.initials: S
authors.lastname: Nakayama
authors.forename: Eisaku
authors.initials: E
authors.lastname: Satoh
authors.forename: Kenji
authors.initials: K
authors.lastname: Iino
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.forename: Sadao
authors.initials: S
authors.lastname: Kuromitsu
authors.forename: Keiichi
authors.initials: K
authors.lastname: Imagawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iijima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D002118:Calcium; D012097:Repressor Proteins; D050052:TRPC Cation Channels; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C096351:transient receptor potential cation channel, subfamily C, member 1