3-methylcholanthrene induces differential recruitment of aryl hydrocarbon receptor to human promoters.

Toxicological Sciences : an Official Journal of the Society of Toxicology
S Safe

Abstract

The paper by Pansoy and coworkers investigates the effects of the aryl hydrocarbon receptor (AHR) ligand 3-methylcholanthrene (3MC) on recruitment of the AHR complex to human promoters in T47D breast cancer cells. The results are particularly important because they can be compared with a prior study using the potent AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the same cell line. The chromatin immunoprecipitation and promoter-focused microarrays (ChIP-chip) demonstrated that after treatment of T47D cells with 1microM 3MC, there were 241 AHR-3MC bound regions and many of these contained AHR-responsive elements. However, they also observed interactions with regions that do not contain these responsive elements, and subsequent analysis of selected target genes show that 3MC-dependent AHR binding did not necessarily predict Ah-responsiveness because induction, repression, and no effects were observed. A prior study with TCDD demonstrated that both 3MC and TCDD induced AHR binding to 127 common regions; however, there were significant differences in ligand (3MC vs. TCDD)-dependent AHR bound regions. The results illustrate the complexity of AHR signaling and also demonstrate that compared with TCDD as a reference ligand, ...Continue Reading

References

Jun 3, 2000·Annual Review of Pharmacology and Toxicology·Y Z GuC A Bradfield
Jan 24, 2003·Annual Review of Pharmacology and Toxicology·Michael S Denison, Scott R Nagy
Jun 1, 2004·Molecular and Cellular Biology·Cédric GouédardYannick Morel
Mar 26, 2008·Nature·Francisco J QuintanaHoward L Weiner
Sep 6, 2008·Journal of Molecular Endocrinology·Stephen Safe, Kyounghyun Kim
Jul 4, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shaimaa AhmedJason Matthews
Nov 11, 2009·Molecular Endocrinology·Carolyn D DuSellDonald P McDonnell
Mar 30, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Andrea PansoyJason Matthews

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