ERα-AHR-ARNT protein-protein interactions mediate estradiol-dependent transrepression of dioxin-inducible gene transcription

Timothy V. Beischlag, Gary H. Perdew

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

The aryl hydrocarbon receptor (AHR) and the aryl hydrocarbon receptor nuclear translocator (ARNT) form a heterodimeric transcription factor upon binding a wide variety of environmental pollutants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AHR target gene activation can be repressed by estrogen and estrogen-like compounds. In this study, we demonstrate that a significant component of TCDD-inducible Cyp1a1 transcription is the result of recruitment of estrogen receptor (ER)-α by AHR/ARNT as a transcriptional corepressor. Both AHR and ARNT were capable of interacting directly with ERα, as ascertained by glutathione S-transferase pull-down. 17/3-estradiol repressed TCDD-activated Cyp1a1 and Cyp1b1 gene transcription in MCF-7 cells in the presence of cycloheximide, as determined by reverse transcription/real-time PCR. Furthermore, chromatin immunoprecipitation (ChIP) assays have shown that ERα is present at the Cyp1a1 enhancer only after co-treatment with E2 and TCDD, in MCF-7 cells. Sequential two-step ChIP assays were performed which demonstrate that AHR and ERα are present together at the same time on the Cyp1a1 enhancer during transrepression. Taken together these data support a role for ER-mediated transrepression of AHR-dependent gene regulation.

Original languageEnglish (US)
Pages (from-to)21607-21611
Number of pages5
JournalJournal of Biological Chemistry
Volume280
Issue number22
DOIs
StatePublished - Jun 3 2005

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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