3-methylcholanthrene induces differential recruitment of aryl hydrocarbon receptor to human promoters.
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.
Safe
Stephen
S
Department of Veterinary Physiology & Physiology, Texas A&M University, College Station, Texas 77843-4466, USA. ssafe@cvm.tamu.edu
D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D006801:Humans; D008748:Methylcholanthrene / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*
D002843:Chromatin; D018336:Receptors, Aryl Hydrocarbon; D008748:Methylcholanthrene