Regulatory role of neuron-restrictive silencing factor in expression of TRPC1.
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.
Ohba
Takayoshi
T
Second Department of Internal Medicine, Akita University School of Medicine, Akita, Japan.
Watanabe
Hiroyuki
H
Takahashi
Yoichiro
Y
Suzuki
Takashi
T
Miyoshi
Ichiro
I
Nakayama
Shinnsuke
S
Satoh
Eisaku
E
Iino
Kenji
K
Sasano
Hironobu
H
Mori
Yasuo
Y
Kuromitsu
Sadao
S
Imagawa
Keiichi
K
Saito
Yoshihiko
Y
Iijima
Toshihiko
T
Ito
Hiroshi
H
Murakami
Manabu
M
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
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