Transcriptional Regulation by Activation and Repression Elements Located at the 5′-Noncoding Region of the Human α9 Nicotinic Receptor Subunit Gene

The α9 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 α9 subunit expression was detected, and in C2C12 cells that do no...

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Published inThe Journal of biological chemistry Vol. 278; no. 39; pp. 37249 - 37255
Main Authors Valor, Luis M., Castillo, Mar, Ortiz, José A., Criado, Manuel
Format Journal Article
LanguageEnglish
Published Elsevier Inc 26.09.2003
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Abstract The α9 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 α9 subunit expression was detected, and in C2C12 cells that do not express α9. 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 α9 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 α9 subunit expression.
AbstractList The α9 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 α9 subunit expression was detected, and in C2C12 cells that do not express α9. 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 α9 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 α9 subunit expression.
Author Castillo, Mar
Ortiz, José A.
Criado, Manuel
Valor, Luis M.
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Snippet The α9 subunit is a component of the neuronal nicotinic acetylcholine receptor gene superfamily that is expressed in very restricted locations. The promoter of...
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Title 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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