Identification and characterization of the promoter region of the Nav1.7 voltage-gated sodium channel gene (SCN9A)
Autor: | Mattia Calissano, David S. Latchman, Mustafa B.A. Djamgoz, D.M. Gascoyne, James K.J. Diss |
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Rok vydání: | 2008 |
Předmět: |
In silico
Molecular Sequence Data Retinoic acid Biology Sodium Channels Mice Neuroblastoma Cellular and Molecular Neuroscience chemistry.chemical_compound Exon Cell Line Tumor Nerve Growth Factor Animals Humans Luciferase RNA Messenger Promoter Regions Genetic Molecular Biology Gene Transcription factor Base Sequence NAV1.7 Voltage-Gated Sodium Channel Promoter Exons Cell Biology Molecular biology Gene Expression Regulation chemistry CpG site Transcription Initiation Site |
Zdroj: | Molecular and Cellular Neuroscience. 37:537-547 |
ISSN: | 1044-7431 |
Popis: | 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). |
Databáze: | OpenAIRE |
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