title: Promoter analysis of mouse Scn3a gene and regulation of the promoter activity by GC box and CpG methylation.
abstract: Voltage-gated sodium channel α-subunit type III (Na(v)1.3) is mainly expressed in the central nervous system and is associated with neurological disorders. The expression of mouse Scn3a product (Na(v)1.3) 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.
authors.affiliation: 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, China.
authors.forename: Guang-Fei
authors.initials: GF
authors.lastname: Deng
authors.forename: Jia-Ming
authors.initials: JM
authors.lastname: Qin
authors.forename: Xun-Sha
authors.initials: XS
authors.lastname: Sun
authors.forename: Zu-Ying
authors.initials: ZY
authors.lastname: Kuang
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.forename: Qi-Hua
authors.initials: QH
authors.lastname: Zhao
authors.forename: Yi-Wu
authors.initials: YW
authors.lastname: Shi
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Liu
authors.forename: Mei-Juan
authors.initials: MJ
authors.lastname: Yu
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Yi
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Liao
authors.forename: Yue-Sheng
authors.initials: YS
authors.lastname: Long
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D062552:NAV1.3 Voltage-Gated Sodium Channel; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D015226:Dinucleoside Phosphates; D062552:NAV1.3 Voltage-Gated Sodium Channel; D015222:Sodium Channels; C515216:Scn3a protein, mouse; C015772:CpG dinucleotide