Analysis of the murine AhR gene promoter

✍ Scribed by Patricia M. Garrison; Michael S. Denison

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 175 KB
• Volume: 14
• Category: Article
• ISSN: 1095-6670
• DOI: 10.1002/(sici)1099-0461(2000)14:1<1::aid-jbt1>3.0.co;2-4

✦ Synopsis

The Ah receptor (AhR) is a ligand-dependent transcription factor that mediates biological and toxicological actions of halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. Although much is known about the biochemical and molecular mechanisms of AhR action, little is known about the factors and events that control expression of the AhR gene itself. The 5-flanking region of the murine AhR gene was characterized and deletion analysis demonstrated that regulatory elements necessary for full constitutive promoter activity are contained within a fragment encompassing ‫481‬ to ‫083‬ of the AhR gene. The murine AhR gene promoter is a GC-rich, TATA-less promoter that whichcontains at least five putative Sp1-like binding sites. Transient transfection experiments not only identified a region between ‫1341‬ and ‫127‬ that represses constitutive promoter activity by 2-to 3-fold, but also demonstrate that basal AhR promoter activity occurs in a cell-and speciesspecific manner. n-Butyrate, a nonspecific histone deacetylase inhibitor, increased AhR promoter activity 8fold, suggesting a role for histone acetylation in AhR gene promoter activity. Overall, this study defines upstream regulatory regions important for constitutive AhR gene expression and identifies a novel activator of AhR gene expression.