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

Mol Cell Biol. 2005 Jul;25(13):5317-28. doi: 10.1128/MCB.25.13.5317-5328.2005.

Abstract

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 co-regulators 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 II (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 alpha (ERalpha) displayed a TCDD- and time-dependent recruitment to the CYP1A1 promoter, which was increased by co-treatment with estradiol. Transfection in HuH7 human liver cells confirmed previously reported ERalpha enhancement of AhR activity. In contrast, TCDD did not induce the recruitment of ERalpha to the estrogen-responsive pS2 promoter, and after 120 min of co-treatment with estradiol, ERalpha is still present on the CYP1A1 promoter but no longer at pS2. RNA interference studies with T47D cells support a role for ERalpha in TCDD-dependent CYP1A1 expression. Our data suggest that ERalpha acts as a coregulator of AhR-mediated transcriptional activation and that the recruitment of ERalpha by AhR represents a novel mechanism AhR-ERalpha cross talk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cytochrome P-450 CYP1A1 / genetics
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / drug effects
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Genes, Reporter
  • Hepatocytes / metabolism
  • Histones / metabolism
  • Humans
  • Kinetics
  • Ligands
  • Luciferases / metabolism
  • Models, Biological
  • Nuclear Receptor Coactivator 2
  • Polychlorinated Dibenzodioxins / pharmacology*
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins pp60(c-src) / genetics
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • RNA Interference
  • Receptor Cross-Talk / drug effects
  • Receptors, Aryl Hydrocarbon / drug effects
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cyclic AMP Response Element-Binding Protein
  • Estrogen Receptor alpha
  • Histones
  • Ligands
  • NCOA2 protein, human
  • Nuclear Receptor Coactivator 2
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • SLA2 protein, human
  • Transcription Factors
  • Estradiol
  • Luciferases
  • Cytochrome P-450 CYP1A1
  • Proto-Oncogene Proteins pp60(c-src)