Role of NRSF/REST in the molecular mechanisms regulating neural-specific expression of trkC/neurotrophin-3 receptor gene
Role of NRSF/REST in the molecular mechanisms regulating neural-specific expression of trkC/neurotrophin-3 receptor gene
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DOI：
10.1016/j.molbrainres.2004.12.019
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发表时间：
2005-04-27
期刊：
影响因子：
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通讯作者：
Matsuoka, I
中科院分区：
文献类型：
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作者：
Nakatani, T;Ueno, S;Matsuoka, I
神经元的分化和发育过程涉及通过指导信号诱导神经元特异性基因，随后是神经营养因子驱动的存活和功能成熟。我们以前已经表明，骨形态发生蛋白-2（BMP-2）和视黄酸协同诱导交感神经元对神经营养因子、神经营养因子3（NT-3）和GDNF的反应，通过上调相应的受体，同时诱导其他神经元特异性基因，包括BRINP 1，一种神经元特异性细胞周期调节蛋白。在本研究中，我们分析了调控TrkC/NT-3受体基因的神经元特异性表达的转录机制。TrkC基因含有至少4个NRSE/RE-1（neuron-restrictive silencing element/repressor element 1）-like元件（TrkC-NRSE A-D）。因此，我们发现在非神经元细胞中，神经元限制性沉默因子（NRSF）作用于位于外显子3下游的TrkC-NRSE D，以类似于NRSF抑制BRINP 1转录的机制的方式抑制TrkC基因的启动子活性。相反，在神经元细胞中，NRSF对TrkC的生物活性被抑制。从这些观察，神经元分化过程中通过NRSE调节神经元特异性基因表达的分子机制进行了讨论。(c)2005 Elsevier B. V.保留所有权利。
The processes of differentiation and development of neurons involve the induction of neuron-specific genes by instructive signals with subsequent neurotrophic factor-driven survival and functional maturation. We have previously shown that bone morphogenetic protein-2 (BMP2) and retinoic acid synergistically induce the responsiveness of developing sympathetic neurons to neurotrophic factors, neurotrophin 3 (NT-3), and GDNF by upregulating corresponding receptors concomitantly with the induction of other neuron-specific genes including BRINP1, a neuron-specific cell-cycle regulatory protein. In the present study, we analyzed transcriptional mechanisms regulating the neuron-specific expression of TrkC/NT-3 receptor gene. TrkC gene contains at least four NRSE/RE-1 (neuron-restrictive silencing element/repressor element 1)-like elements (TrkC-NRSE A-D). Consequently, we found that in non-neuronal cells, neuron-restrictive silencing factor (NRSF) acts on TrkC-NRSE D located at the downstream of exon 3 to suppress the promoter activity of TrkC gene in a manner similar to the mechanism of NRSF suppressing BRINP1 transcription. In contrast, in neuronal cells, the biological activity of NRSF on TrkC was suppressed. From these observations, molecular mechanisms regulating the expression of neuron-specific genes via NRSE during neuronal differentiation are discussed. (c) 2005 Elsevier B.V. All rights reserved.