Regulatory role of neuron-restrictive silencing factor in expression of TRPC1
Regulatory role of neuron-restrictive silencing factor in expression of TRPC1
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DOI：
10.1016/j.bbrc.2006.10.107
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发表时间：
2006-12-22
影响因子：
3.1
通讯作者：
Murakami, Manabu
中科院分区：
文献类型：
--
作者：
Ohba, Takayoshi;Watanabe, Hiroyuki;Murakami, Manabu
神经元限制性沉默因子（NRSF）结合其共有元件抑制多种基因的转录。显性负性形式（dnNRSF）通过一种未知的机制对心脏发生具有肥大作用。我们研究了瞬时受体电位（TRP）通道蛋白的参与，使用过表达dnNRSF的转基因小鼠（dnNRSF小鼠）。电泳迁移率变动分析揭示了NRSF和TRPC 1基因组DNA内含子4中的神经元限制性沉默元件样序列之间的相互作用。RT-PCR和Western分析结果表明，TRPC 1在dnNRSF小鼠心脏中表达上调。TRPC 1在HEK 293 T细胞中的瞬时过表达增加了活化T细胞核因子（NFAT）启动子的活性，并刺激了钙池操纵的Ca 2+通道（SOCC）介导的Ca 2+进入。将TRPC 1转染到原代心肌细胞中可以增加NFAT活性，表明TRPC 1在NFAT激活中发挥重要作用。我们的研究结果强烈表明，NRSF调节TRP 1基因的表达，并导致通过SOCC的钙进入水平的变化。(c)2006年爱思唯尔公司All rights reserved.
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 Ca2+ channel (SOCC)-mediated Ca2+ 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. (c) 2006 Elsevier Inc. All rights reserved.