Hormone receptor associated epigenetic reprogramming as a mediator of environmental exposure in women's health

激素受体相关的表观遗传重编程作为女性健康环境暴露的中介

• 批准号: 10924998
• 负责人: Elizabeth Martin
• 金额: $ 113.83万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10924998
• 关键词: Binding; Biochemistry; Breast Cancer Risk Factor; Cells; Chromatin Structure; Diethylhexyl Phthalate; Disease; Environmental Exposure; Environmental Risk Factor; Epigenetic Process; Goals; Hormonal Change; Hormone Receptor; Ligand Binding Domain; Ligands; Mediator; Phenotype; Pregnancy; Progesterone; Progesterone Receptors; Proteins; Research; T47D; Women' s Health; experimental study; follow-up; maternal risk; mono-(2-ethylhexyl)phthalate; phthalates; programs; receptor; receptor expression; synergism; transcription factor; transcriptomics

In addition to demonstrating that phthalates can impact the phenotype,of T47D cells in culture, we have characterized differences in phthalates binding to PR and the impact exposure has on progesterone receptor expression. Specifically we have shown that progesterone receptor is stabilized in the presence of the phthalate mixture with endogenous progesterone in a synergistic way. As a follow up to this, we performed biochemistry experiments and have found that neither MEHP and DEHP bind directly to the ligand binding domain of PR. These findings have lead us to try and understand whether the observed synergism at the protein level correlates to changes at the transcriptomic level and changes to chromatin structure.

除了证明邻苯二甲酸盐可以影响培养中的 T47D 细胞的表型外，我们还表征了邻苯二甲酸盐与 PR 结合的差异以及暴露对孕酮受体表达的影响。具体来说，我们已经表明，在邻苯二甲酸酯混合物与内源性孕酮的存在下，孕酮受体以协同方式稳定。随后，我们进行了生物化学实验，发现 MEHP 和 DEHP 都不直接与 PR 的配体结合结构域结合。这些发现促使我们尝试了解在蛋白质水平上观察到的协同作用是否与转录组水平的变化和染色质结构的变化相关。