ER alpha-AHR-ARNT protein-protein interactions mediate estradiol-dependent transrepression of dioxin-inducible gene transcription.
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)-alpha by AHR/ARNT as a transcriptional co-repressor. Both AHR and ARNT were capable of interacting directly with ER alpha, as ascertained by glutathione S-transferase pull-down. 17Beta-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 ER alpha 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 ER alpha 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.
Mesh Terms:
Aryl Hydrocarbon Receptor Nuclear Translocator, Blotting, Western, Cell Line, Tumor, Chromatin Immunoprecipitation, Cycloheximide, Cytochrome P-450 CYP1A1, DNA-Binding Proteins, Dioxins, Enhancer Elements, Genetic, Environmental Pollution, Estrogen Receptor alpha, Gene Expression Regulation, Genes, Reporter, Glutathione Transferase, Humans, Plasmids, Protein Binding, Receptors, Aryl Hydrocarbon, Reverse Transcriptase Polymerase Chain Reaction, Tetrachlorodibenzodioxin, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection
Aryl Hydrocarbon Receptor Nuclear Translocator, Blotting, Western, Cell Line, Tumor, Chromatin Immunoprecipitation, Cycloheximide, Cytochrome P-450 CYP1A1, DNA-Binding Proteins, Dioxins, Enhancer Elements, Genetic, Environmental Pollution, Estrogen Receptor alpha, Gene Expression Regulation, Genes, Reporter, Glutathione Transferase, Humans, Plasmids, Protein Binding, Receptors, Aryl Hydrocarbon, Reverse Transcriptase Polymerase Chain Reaction, Tetrachlorodibenzodioxin, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection
J. Biol. Chem.
Date: Jun. 03, 2005
PubMed ID: 15837795
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