Journal Article

3-Methylcholanthrene Induces Differential Recruitment of Aryl Hydrocarbon Receptor to Human Promoters

Stephen Safe

in Toxicological Sciences

Volume 117, issue 1, pages 1-3
Published in print September 2010 | ISSN: 1096-6080
Published online July 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq193
3-Methylcholanthrene Induces Differential Recruitment of Aryl Hydrocarbon Receptor to Human Promoters

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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 1μM 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, 3MC is a selective AHR modulator.

Keywords: AhR; ChIP; AhR binding sites; ligand differences

Journal Article.  1442 words. 

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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