金雀异黄素和双酚 A 导致雌激素受体 1 以细胞特异性的方式绑定上千个位点_杰森

针对病种：子宫癌

发表时间：2012年9月

发表国家：美国

登载刊物：基因组研究

研究单位：美国亚拉巴马州哈森阿尔法生物技术研究院；美国纽约医科大学泌尿外科微生物学系

研究人员：杰森格茨，蒂莫西 E瑞迪，凯瑟琳 E 瓦利，等

主要结论：总体来看，这两种外源雌激素通过 ESR1 在全基因组范围内明显调节了基因的表达，即使与内源性雌激素E2相比，其较低的功效会导致较少的 ESR1 绑定位点和更少的基因表达的变化.

Genome Research, 2012, 22(11):2153-2162.

Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner

Jason Gertz, Timothy E. Reddy, Katherine E. Varley, et al

HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA; Department of Microbiology, Department of Urology, NYU School of Medicine, New York, New York 10016, USA

Endogenous estrogens that are synthesized in the body impact gene regulation by activating estrogen receptors in diverse cell types. Exogenous compounds that have estrogenic properties can also be found circulating in the blood in both children and adults. The genome-wide impact of these environmental estrogens on gene regulation is unclear. To obtain an integrated view of gene regulation in response to environmental and endogenous estrogens on a genome-wide scale, we performed ChIP-seq to identify estrogen receptor 1 (ESR1; previously estrogen receptor α) binding sites, and RNA-seq in endometrial cancer cells exposed to bisphenol A (BPA; found in plastics), genistein (GEN; found in soybean), or 17β-estradiol (E2; an endogenous estrogen). GEN and BPA treatment induces thousands of ESR1 binding sites and >50 gene expression changes, representing a subset of E2-induced gene regulation changes. Genes affected by E2 were highly enriched for ribosome-associated proteins; however, GEN and BPA failed to regulate most ribosome-associated proteins and instead enriched for transporters of carboxylic acids. Treatment-dependent changes in gene expression were associated with treatment-dependent ESR1 binding sites, with the exception that many genes up-regulated by E2 harbored a BPA-induced ESR1 binding site but failed to show any expression change after BPA treatment. GEN and BPA exhibited a similar relationship to E2 in the breast cancer line T-47D, where cell type specificity played a much larger role than treatment specificity. Overall, both environmental estrogens clearly regulate gene expression through ESR1 on a genome-wide scale, although with lower potency resulting in less ESR1 binding sites and less gene expression changes compared to the endogenous estrogen, E2.

美国《基因组研究》，2012年9月

金雀异黄素和双酚 A 导致雌激素受体 1 以细胞特异性的方式绑定上千个位点

杰森格茨，蒂莫西 E瑞迪，凯瑟琳 E 瓦利，等

美国亚拉巴马州哈森阿尔法生物技术研究院；美国纽约医科大学泌尿外科微生物学系

在体内合成的内源性雌激素通过在不同类型的细胞中活化雌激素受体来影响基因调控。在儿童和成人的血液循环中发现外源化合物具有雌激素特性。这些外源雌激素对基因调控的全基因组作用尚不清楚。为了获得响应外源和内源性雌激素全基因组规模的基因调控的集成视图，我们进行了ChIP-seq测试来确定雌激素受体 1 （ESR1; 以前的雌激素受体 α）结合位点，以及RNA-seq在子宫内膜癌细胞中暴露于双酚 A (BPA; 在塑料产品中发现)，金雀异黄素（GEN;在大豆中发现），或 17 β-雌二醇（E2; 内源性雌激素）。GEN和双酚 A 的治疗诱导数以千计的 ESR1 结合位点和 > 50的基因表达变化，代表 E2 诱导的基因调控变化的子集。受 E2影响的基因在核糖体相关蛋白中高度浓缩；然而，GEN和BPA 未能调节大多数核糖体相关蛋白质，反而丰富了羧酸转运蛋白。依赖性治疗基因表达的变化与依赖性治疗 ESR1 的结合位点有关，除非由 E2上调的许多基因含有BPA 诱导的 ESR1 结合位点，否则在经过BPA 治疗后未能出现任何表达的变化。GEN和BPA在乳腺癌 T-47D细胞中表现出与E2相似的关系，其中细胞类型特异性的作用明显大于特异性治疗。总体来看，这两种外源雌激素通过 ESR1 在全基因组范围内明显调节了基因的表达，即使与内源性雌激素E2相比，其较低的功效会导致较少的 ESR1 绑定位点和更少的基因表达的变化。