Abstract |
Estrogen signaling can occur through a nonclassical pathway involving the interaction of estrogen receptors (ER) with other transcription factors such as activator protein-1 (AP-1) and SP-1. However, there is little mechanistic understanding about this pathway, with conflicting results from in vitro investigations. In this study, we applied the ChIP-on-chip approach to identify ERbeta-binding sites on a genome-wide scale, identifying 1,457 high-confidence binding sites in ERbeta-overexpressing MCF7 breast cancer cells. Genes containing ERbeta-binding sites can be regulated by E2. Notably, approximately 60% of the genomic regions bound by ERbeta contained AP-1-like binding regions and estrogen response element-like sites, suggesting a functional association between AP-1 and ERbeta signaling. Chromatin immunoprecipitation (ChIP) analysis confirmed the association of AP-1, which is composed of the oncogenic transcription factors c-Fos and c-Jun, to ERbeta-bound DNA regions. Using a re-ChIP assay, we showed co-occupancy of ERbeta and AP-1 on chromatin. Short interfering RNA-mediated knockdown of c-Fos or c-Jun expression decreased ERbeta recruitment to chromatin, consistent with the role of AP-1 in mediating estrogen signaling in breast cancer cells. Additionally, ERalpha and ERbeta recruitment to AP-1/ ERbeta target regions exhibited gene-dependent differences in response to antiestrogens. Together, our results broaden insights into ERbeta DNA-binding at the genomic level by revealing crosstalk with the AP-1 transcription factor.
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Authors | Chunyan Zhao, Hui Gao, Yawen Liu, Zoi Papoutsi, Sadaf Jaffrey, Jan-Ake Gustafsson, Karin Dahlman-Wright |
Journal | Cancer research
(Cancer Res)
Vol. 70
Issue 12
Pg. 5174-83
(Jun 15 2010)
ISSN: 1538-7445 [Electronic] United States |
PMID | 20501845
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chromatin
- Estrogen Receptor beta
- Estrogens
- RNA, Messenger
- Transcription Factor AP-1
- Luciferases
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Topics |
- Blotting, Western
- Breast Neoplasms
(genetics, metabolism, pathology)
- Cell Line, Tumor
- Cell Proliferation
- Chromatin
(metabolism)
- Chromatin Immunoprecipitation
- Estrogen Receptor beta
(genetics, metabolism)
- Estrogens
(pharmacology)
- Female
- Genome, Human
- Humans
- Luciferases
(metabolism)
- Promoter Regions, Genetic
(genetics)
- RNA, Messenger
(genetics, metabolism)
- Response Elements
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
- Transcription Factor AP-1
(genetics, metabolism)
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