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Promoter Analysis of Mouse Scn3a Gene and Regulation of the Promoter Activity by GC Box and CpG Methylation

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Abstract

Voltage-gated sodium channel α-subunit type III (Nav1.3) is mainly expressed in the central nervous system and is associated with neurological disorders. The expression of mouse Scn3a product (Nav1.3) mainly occurs in embryonic and early postnatal brain but not in adult brain. Here, we report for the first time the identification and characterization of the mouse Scn3a gene promoter region and regulation of the promoter activity by GC box and CpG methylation. Luciferase assay showed that the promoter region F1.2 (nt −1,049 to +157) had significantly higher activity in PC12 cells, comparing with that in SH-SY5Y cells and HEK293 cells. A stepwise 5′ truncation of the promoter region found that the minimal functional promoter located within the region nt −168 to +157. Deletion of a GC box (nt −254 to −258) in the mouse Scn3a promoter decreased the promoter activity. CpG methylation of the F1.2 without the GC box completely repressed the promoter activity, suggesting that the GC box is a critical element in the CpG-methylated Scn3a promoter. These results suggest that the GC box and CpG methylation might play important roles in regulating mouse Scn3a gene expression.

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Acknowledgments

We would like to thank an anonymous reviewer for her/his critical and constructive comments that led to the improvement of this paper. This work was supported by The National Natural Science Foundation of China (grant nos. 31700928, 30600198, 30870876, 81000558, 81071045, 30700247, and 30900451) and The Guangzhou Scholar Project (grant nos. 10A011G and 10A012G). We are grateful to the He Shanheng Charity Foundation for contributing to the development of this institute.

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  1. Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and The Ministry of Education of China, Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, 250 Chang-gang-dong Road, Guangzhou, 510260, China

    Guang-Fei Deng, Jia-Ming Qin, Xun-Sha Sun, Zu-Ying Kuang, Tao Su, Qi-Hua Zhao, Yi-Wu Shi, Xiao-Rong Liu, Mei-Juan Yu, Yong-Hong Yi, Wei-Ping Liao & Yue-Sheng Long

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  1. Guang-Fei Deng
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  2. Jia-Ming Qin
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Correspondence to Yue-Sheng Long.

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Guang-Fei Deng and Jia-Ming Qin contributed equally to this work.

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Deng, GF., Qin, JM., Sun, XS. et al. Promoter Analysis of Mouse Scn3a Gene and Regulation of the Promoter Activity by GC Box and CpG Methylation. J Mol Neurosci 44, 115–121 (2011). https://doi.org/10.1007/s12031-011-9492-8

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  • DOI: https://doi.org/10.1007/s12031-011-9492-8

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