Aryl hydrocarbon receptor-mediated transcription:: Ligand-dependent recruitment of estrogen receptor α to 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive promoters

Using chromatin immunoprecipitation assays, we studied the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)mediated recruitment of the aryl hydrocarbon receptor (AhR) and several coregulators to the CYP1A1 promoter. AhR displayed a time-dependent recruitment, reaching a peak at 75 min and maintaining promoter occupancy for the remainder of the time course. Recruitment of AhR was followed by TIF2/SRC2, which preceded CBP, histone H3 acetylation, and RNA polymerase 11 (RNAPII). Simultaneous recruitment to the enhancer and the TATA box region suggests the formation of a large multiprotein complex bridging the two promoter regions. Interestingly, estrogen receptor et (ER alpha) displayed a TCDD- and time-dependent recruitment to the CYP1A1 promoter, which was increased by cotreatment with estradiol. Transfection in HuH7 human liver cells confirmed previously reported ER alpha enhancement of AhR activity. In contrast, TCDD did not induce the recruitment of ER alpha to the estrogen-responsive pS2 promoter, and after 120 min of cotreatment with estradiol, ER alpha is still present on the CYP1A1 promoter but no longer at pS2. RNA interference studies with T47D cells support a role for ER alpha in TCDD-dependent CYP1A1 expression. Our data suggest that ER alpha acts as a coregulator of AhR-mediated transcriptional activation and that the recruitment of ER(x by AhR represents a novel mechanism AhR-ER alpha cross talk.