Chromatin Dynamics of Endocrine Disruptor Compounds on Estrogen Receptor Function

女性一生中暴露于雌激素是乳腺癌发展的一个关键风险因素。 许多环境化合物，称为内分泌干扰化合物（EDCs）已被证明 结合并激活雌激素受体，因此与乳腺癌肿瘤发生有关。然而，在这方面， 已经清楚的是，雌激素受体的EDC激活诱导配体特异性转录， 程序.我们的假设是，染色质结构是内分泌干扰作用的关键调节因子， 乳腺癌的发展和进展。在这个建议中，我们将使用一个公正的基因组方法， 表征用双酚A和染料木黄酮处理后乳腺癌细胞中的染色质结构。 将表征EDC响应区的染色质修饰和核小体定位。 最后，长期暴露于双酚A和染料木素对雌激素受体募集的影响 将被审查。这些研究将阐明内分泌干扰物引起特异性转录的机制， 胸部的轮廓

A woman's overall lifetime exposure to estrogen is a critical risk factor for the development of breast cancer. A number of environmental compounds, termed endocrine disrupting compounds (EDCs) have been shown to bind and activate the estrogen receptor and are thus implicated in breast cancer tumorigenesis. However, it has become clear that EDC activation of the estrogen receptor induces ligand-specific transcriptional programs. It is our hypothesis that chromatin structure is a key regulator of endocrine, disruptor action in breast cancer development and progression. In this proposal, we will use an unbiased genomic approach to characterize chromatin structure in breast cancer cells following treatment with bisphenol A and genistein. EDC responsive regions will be characterized for chromatin modifications and nucleosome positioning. Finally, the effects of long term exposure to both bisphenol A and genistein on estrogen receptor recruitment will be examined. These studies will clarify the mechanisms by which EDCs elicit specific transcriptional profiles in the breast.