Transcriptional regulation by activation and repression elements located at the 5′-noncoding region of the human α9 nicotinic receptor subunit gene
Transcriptional regulation by activation and repression elements located at the 5′-noncoding region of the human α9 nicotinic receptor subunit gene
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DOI：
10.1074/jbc.m307043200
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发表时间：
2003-09-26
影响因子：
4.8
通讯作者：
Criado, M
中科院分区：
文献类型：
--
作者：
Valor, LM;Castillo, M;Criado, M
α9亚基是神经性烟碱型乙酰胆碱受体基因超家族的一个组成部分，在非常有限的位置表达。人类基因的启动子已经在人类神经母细胞瘤SH-SY5Y中进行了分析，其中检测到α9亚单位的表达，并在不表达α9的C2C12细胞中进行了分析。在SH-SY5Y细胞中，近端启动子区域(-322~+113)的转录活性最高，而在C1C12细胞中，其转录活性较低。位于5‘-非编码区的两个元件表现出相反的作用。位于+15和+48之间的负元件似乎是细胞特异性的，因为它在C2C12细胞中有效，但在SH-SY5Y细胞中无效，在SH-SY5Y细胞中，它被启动子区域5‘的存在抵消。位于+66和+79之间的激活元件由两个相邻的SOX盒形成，使α9启动子的活性增加约4倍，甚至能够激活其他启动子。该元件与SOX蛋白相互作用，可能是通过一种合作机制，其中两个SOX盒是必要的。我们认为，SOX复合体提供了一个初始的支架，促进了负责α9亚单位表达的转录机制的招募。
The alpha9 subunit is a component of the neuronal nicotinic acetylcholine receptor gene superfamily that is expressed in very restricted locations. The promoter of the human gene has been analyzed in the human neuroblastoma SH-SY5Y, where alpha9 subunit expression was detected, and in C2C12 cells that do not express alpha9. A proximal promoter region ( from - 322 to + 113) showed maximal transcriptional activity in SH-SY5Y cells, whereas its activity in C1C12 cells was much lower. Two elements unusually located at the 5'-noncoding region exhibited opposite roles. A negative element located between + 15 and + 48 appears to be cell-specific because it was effective in C2C12 but not in SH-SY5Y cells, where it was counterbalanced by the presence of the promoter region 5' to the initiation site. An activating element located between + 66 and + 79 and formed by two adjacent Sox boxes increased the activity of the alpha9 promoter about 4-fold and was even able to activate other promoters. This element interacts with Sox proteins, probably through a cooperative mechanism in which the two Sox boxes are necessary. We propose that the Sox complex provides an initial scaffold that facilitates the recruiting of the transcriptional machinery responsible for alpha9 subunit expression.