Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Cancer Res. 2013 Aug 15;73(16):5130-9. doi: 10.1158/0008-5472.CAN-13-0742. Epub 2013 Jun 26.
Cross-talk between estrogen receptors (ER) and glucocorticoid receptors (GR) has been shown to contribute to the development and progression of breast cancer. Importantly, the ER and GR status in breast cancer cells is a significant factor in determining the outcome of the disease. However, mechanistic details defining the cellular interactions between ER and GR are poorly understood. We investigated genome-wide binding profiles for ER and GR upon coactivation and characterized the status of the chromatin landscape. We describe a novel mechanism dictating the molecular interplay between ER and GR. Upon induction, GR modulates access of ER to specific sites in the genome by reorganization of the chromatin configuration for these elements. Binding to these newly accessible sites occurs either by direct recognition of ER response elements or indirectly through interactions with other factors. The unveiling of this mechanism is important for understanding cellular interactions between ER and GR and may represent a general mechanism for cross-talk between nuclear receptors in human disease.
雌激素受体 (ER) 和糖皮质激素受体 (GR) 之间的串扰已被证明有助于乳腺癌的发展和进展。重要的是，乳腺癌细胞中 ER 和 GR 的状态是决定疾病结局的重要因素。然而，定义 ER 和 GR 之间细胞相互作用的机制细节知之甚少。我们研究了 ER 和 GR 共同激活时的全基因组结合谱，并描述了决定 ER 和 GR 之间分子相互作用的新机制。诱导后，GR 通过重新组织这些元件的染色质构象，调节 ER 对基因组中特定位点的可及性。与这些新可及位点的结合可以通过 ER 反应元件的直接识别或通过与其他因子的间接相互作用发生。揭示这种机制对于理解 ER 和 GR 之间的细胞相互作用很重要，并且可能代表人类疾病中核受体之间串扰的一般机制。
