Analysis of the murine AhR gene promoter

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 contains 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. © 1999 John Wiley & Sons, Inc. J Biochem Toxicol 14: 1–10, 2000

Glucocorticoid-Enhanced Expression of Dioxin Target Genes through Regulation of the Rat Aryl Hydrocarbon Receptor

“…Murine AhR promoter analysis revealed a GC-rich, TATA-less promoter containing five putative Sp1-like binding sites (Garrison and Denison, 2000), well conserved in the human AhR promoter (Eguchi et al, 1994). In addition, a putative XRE was reported for the murine AhR promoter (Garrison and Denison, 2000). In our study, two GRE-like sequences were found that were specific for the rodent Ahr genes.…”

“…The GR-mediated upregulation of AhR is probably due to the presence of GREs in the rat AhR promoter but not in the human AhR promoter (this study). Murine AhR promoter analysis revealed a GC-rich, TATA-less promoter containing five putative Sp1-like binding sites (Garrison and Denison, 2000), well conserved in the human AhR promoter (Eguchi et al, 1994). In addition, a putative XRE was reported for the murine AhR promoter (Garrison and Denison, 2000).…”

FSH/LH-Dependent Upregulation of Ahr in Murine Granulosa Cells Is Controlled by PKA Signaling and Involves Epigenetic Regulation

“…We intended to investigate whether PMSG has an effect on Ahr promoter activity by measuring luciferase activity in GCs transfected with Ahr -promoter reporter constructs. Although it is now widely accepted that regulatory sequences necessary for promoter activity and gene expression can be located far from TSS, the promoter sequence used in this study has been shown to contain essential elements for constitutive murine Ahr promoter activity [50,51]. Although promoter activity was detected in non-treated cells, we did not see an additional increase in response to PMSG in these transiently transfected cells (Figure 5c).…”

“…Ahr promoter is known to contain several regulatory elements that can be targeted by downstream modulators of gonadotropin activity [50,51]. To study if PMSG induces Ahr expression via increased promoter activity, we transfected GCs from non-treated immature mice with a luciferase reporter construct containing Ahr promoter site.…”

Transcriptional Regulation of the AhR Gene during Adipose Differentiation

“…Several reports revealed that the sequence Ϫ378/Ϫ359 is likely not necessary for constitutive AhR expression. 36,42) Thus the sequence identified in this study plays the specific role in AhR expression in preadipocytes. The results shown in Fig.…”