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 language | English (US) |
|---|---|
| Pages (from-to) | 1-10 |
| Number of pages | 10 |
| Journal | Journal of Biochemical and Molecular Toxicology |
| Volume | 14 |
| Issue number | 1 |
| State | Published - 2000 |
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Keywords
- Ah Receptor
- Arnt
- PAS
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Health, Toxicology and Mutagenesis
- Toxicology
Cite this
Analysis of the murine AhR gene promoter. / Garrison, Patricia M.; Denison, Michael S.
In: Journal of Biochemical and Molecular Toxicology, Vol. 14, No. 1, 2000, p. 1-10.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Analysis of the murine AhR gene promoter
AU - Garrison, Patricia M.
AU - Denison, Michael S.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Ah Receptor
KW - Arnt
KW - PAS
UR - http://www.scopus.com/inward/record.url?scp=0033988723&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033988723&partnerID=8YFLogxK
M3 - Article
C2 - 10561076
AN - SCOPUS:0033988723
VL - 14
SP - 1
EP - 10
JO - Journal of Biochemical and Molecular Toxicology
JF - Journal of Biochemical and Molecular Toxicology
SN - 1095-6670
IS - 1
ER -