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AP‐2γ regulates oestrogen receptor‐mediated long‐range chromatin interaction and gene transcription
Author(s) -
Tan Si Kee,
Lin Zhen Hua,
Chang Cheng Wei,
Varang Vipin,
Chng Kern Rei,
Pan You Fu,
Yong Eu Leong,
Sung Wing Kin,
Cheung Edwin
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.151
Subject(s) - foxa1 , biology , chromatin , transcription factor , chia pet , pioneer factor , enhancer , genetics , microbiology and biotechnology , chromatin remodeling , gene
Oestrogen receptor α (ERα) is key player in the progression of breast cancer. Recently, the cistrome and interactome of ERα were mapped in breast cancer cells, revealing the importance of spatial organization in oestrogen‐mediated transcription. However, the underlying mechanism of this process is unclear. Here, we show that ERα binding sites (ERBS) identified from the Chromatin Interaction Analysis‐Paired End DiTag of ERα are enriched for AP‐2 motifs. We demonstrate the transcription factor, AP‐2γ, which has been implicated in breast cancer oncogenesis, binds to ERBS in a ligand‐independent manner. Furthermore, perturbation of AP‐2γ expression impaired ERα DNA binding, long‐range chromatin interactions, and gene transcription. In genome‐wide analyses, we show that a large number of AP‐2γ and ERα binding events converge together across the genome. The majority of these shared regions are also occupied by the pioneer factor, FoxA1. Molecular studies indicate there is functional interplay between AP‐2γ and FoxA1. Finally, we show that most ERBS associated with long‐range chromatin interactions are colocalized with AP‐2γ and FoxA1. Together, our results suggest AP‐2γ is a novel collaborative factor in ERα‐mediated transcription.