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Mol Cell Neurosci. 2008 Mar;37(3):537-47. doi: 10.1016/j.mcn.2007.12.002. Epub 2007 Dec 15.

Identification and characterization of the promoter region of the Nav1.7 voltage-gated sodium channel gene (SCN9A).

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  • 1Medical Molecular Biology Unit, Institute of Child Health, University College London, Guilford Street, London WC1N 1EH, UK. j.diss@ich.ucl.ac.uk

Abstract

The Nav1.7 sodium channel plays an important role in pain and is also upregulated in prostate cancer. To investigate the mechanisms regulating physiological and pathophysiological Nav1.7 expression we identified the core promoter of this gene (SCN9A) in the human genome. In silico genomic analysis revealed a putative SCN9A 5' non-coding exon approximately 64,000 nucleotides from the translation start site, expression of which commenced at three very closely-positioned transcription initiation sites (TISs), as determined by 5' RACE experiments. The genomic region around these TISs possesses numerous core elements of a TATA-less promoter within a well-defined CpG island. Importantly, it acted as a promoter when inserted upstream of luciferase in a fusion construct. Moreover, the activity of the promoter-luciferase construct ostensibly paralleled endogenous Nav1.7 mRNA levels in vitro, with both increased in a quantitatively and qualitatively similar manner by numerous factors (including NGF, phorbol esters, retinoic acid, and Brn-3a transcription factor over-expression).

PMID:
18249135
[PubMed - indexed for MEDLINE]
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