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

Toxicol Sci. 2010 Sep;117(1):1-3. doi: 10.1093/toxsci/kfq193. Epub 2010 Jul 22.

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, 3MC is a selective AHR modulator.

Publication types

  • Comment
  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatin / metabolism
  • Chromatin Immunoprecipitation
  • Humans
  • Methylcholanthrene / toxicity*
  • Promoter Regions, Genetic*
  • Receptors, Aryl Hydrocarbon / metabolism*

Substances

  • Chromatin
  • Receptors, Aryl Hydrocarbon
  • Methylcholanthrene