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Title: AP-2? regulates estrogen receptor-mediated long-range chromatin interactions and gene transcription
Authors: TAN SI KEE
Keywords: AP-2γ, ERα, FoxA1, ChIA-PET, ChIP-Seq, Chromatin
Issue Date: 16-Jul-2012
Citation: TAN SI KEE (2012-07-16). AP-2? regulates estrogen receptor-mediated long-range chromatin interactions and gene transcription. ScholarBank@NUS Repository.
Abstract: Estrogen receptor alpha (ERalpha) is a key player in breast cancer progression. Recently, ERalpha cistrome and interactome were mapped in MCF-7 cells, revealing the importance of spatial chromatin organization in estrogen-mediated transcription. Our study revealed that ERalpha binding sites (ERBS) identified from Chromatin Interaction Analysis-Paired End DiTag (ChIA-PET) are enriched of AP-2 motifs. AP-2gamma, a transcription factor associated with breast cancer, binds to ERBS harboring AP-2 motifs in a ligand-independent manner. Perturbation of AP-2gamma expression impaired ERalpha DNA binding, long-range chromatin interactions and gene transcription. In our genome-wide analyses, a large number AP-2gamma and ERalpha binding events converge together across the genome. Majority of these shared regions are also occupied by a pioneer factor, FoxA1. Functional interplay between AP-2gamma and FoxA1 was further demonstrated. Finally, ERBS associated with long-range chromatin interactions preferentially co-localize with AP-2gamma and FoxA1. Together, our results suggest that AP-2gamma is a novel ERalpha collaborative factor.
Appears in Collections:Ph.D Theses (Open)

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