Analysis of the murine AhR gene promoter

Patricia M. Garrison, Michael S. Denison

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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 -184 to +380 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 -1431 and -721 that represses constitutive promoter activity by 2- to 3-fold, but also demonstrate that basal AhR promoter activity occurs in a cell- and species-specific manner. n-Butyrate, a nonspecific histone deacetylase inhibitor, increased AhR promoter activity 8-fold, 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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalJournal of Biochemical and Molecular Toxicology
Volume14
Issue number1
StatePublished - 2000

Keywords

  • Ah Receptor
  • Arnt
  • PAS

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Health, Toxicology and Mutagenesis
  • Toxicology

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