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首页> 外文期刊>EMBO Journal >AP-2gamma regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.
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AP-2gamma regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.

机译：AP-2gamma调节雌激素受体介导远程交互和基因染色质转录。

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Oestrogen receptor alpha (ERalpha) is key player in the progression of breast cancer. Recently, the cistrome and interactome of ERalpha 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 ERalpha binding sites (ERBS) identified from the Chromatin Interaction Analysis-Paired End DiTag of ERalpha are enriched for AP-2 motifs. We demonstrate the transcription factor, AP-2gamma, which has been implicated in breast cancer oncogenesis, binds to ERBS in a ligand-independent manner. Furthermore, perturbation of AP-2gamma expression impaired ERalpha DNA binding, long-range chromatin interactions, and gene transcription. In genome-wide analyses, we show that a large number of AP-2gamma and ERalpha 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-2gamma and FoxA1. Finally, we show that most ERBS associated with long-range chromatin interactions are colocalized with AP-2gamma and FoxA1. Together, our results suggest AP-2gamma is a novel collaborative factor in ERalpha-mediated transcription.
机译：雌激素受体α(ERalpha)是关键的球员在乳腺癌的进展。的cistrome和interactome ERalpha映射在乳腺癌细胞中,揭示了空间组织的重要性oestrogen-mediated转录。这个过程的潜在机制还不清楚。在这里,我们表明,ERalpha结合位点(erb)确定的染色质交互Analysis-Paired结束DiTag ERalpha丰富AP-2图案。因素,AP-2gamma已经涉及乳腺癌肿瘤形成,结合erbligand-independent方式。微扰AP-2gamma表达受损ERalpha DNA结合,远程染色质相互作用和基因转录。全基因组分析,我们表明,大量AP-2gamma和ERalpha绑定事件的收敛在整个基因组。共享区域也被先锋因素,FoxA1。AP-2gamma功能相互影响FoxA1。与远程染色质交互与AP-2gamma和FoxA1。我们的研究结果表明AP-2gamma一部小说ERalpha-mediated合作的因素转录。

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