Developmental regulation of estrogen receptor-alpha by epigenetic modification

表观遗传修饰对雌激素受体-α的发育调节

• 批准号: 0919944
• 负责人: Melinda Wilson
• 金额: $ 59.19万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0919944&HistoricalAwards=false
• 关键词: Developmental; regulation; estrogen; receptor; alpha

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).This study investigates the molecular mechanisms by which critical genes are regulated in the developing brain. Exposure to the hormone estrogen during development is critical for establishing long-term structural and functional aspects of the brain. Estrogen acts through receptor proteins inside cells that mediate its action. Estrogen receptor gene expression is developmentally regulated, but the molecular mechanisms that regulate this expression are not known. In this study, the effects of epigenetic modification of DNA on the developmental expression of estrogen receptors will be examined in a mouse animal model. Molecular biology techniques are used to identify these changes. It is hypothesized that estrogen receptor gene expression is shut off by DNA methylation during development. The results of this study will enhance the understanding of the regulation of gene expression in the brain at different developmental stages, as these changes can have long-lasting consequences in brain function in adulthood. This study combines the fields of neuroendocrinology with the rapidly growing field of epigenetics. In addition to the answering fundamental questions in the field of developmental neuroscience, the impact of this study is enhanced by the involvement of multiple undergraduate, graduate, and postdoctoral students over the course of the study that provides a fundamental scientific background and training for these students. The students will be involved in all aspects of this project from performing experiments to presenting the findings at University events as well as at other regional and national meetings. Students will also have the opportunity participate in community events such as those associated with Brain Awareness Week with the Society for Neuroscience. These events allow students to interact with the public to educate children and parents alike to the importance of understanding how their brains function.

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。这项研究调查了发育中大脑中调控关键基因的分子机制。 在发育过程中暴露于雌激素对于建立大脑的长期结构和功能方面至关重要。 雌激素通过细胞内的受体蛋白介导其作用。 雌激素受体基因的表达受发育调控，但调控这种表达的分子机制尚不清楚。 在这项研究中，将在小鼠动物模型中检查DNA的表观遗传修饰对雌激素受体发育表达的影响。 分子生物学技术用于识别这些变化。 据推测，雌激素受体基因表达在发育过程中被DNA甲基化关闭。 这项研究的结果将增强对不同发育阶段大脑基因表达调控的理解，因为这些变化可能对成年后的大脑功能产生长期影响。 这项研究将神经内分泌学领域与快速发展的表观遗传学领域相结合。 除了回答发展神经科学领域的基本问题外，本研究的影响还通过多名本科生，研究生和博士后学生在研究过程中的参与来增强，为这些学生提供基本的科学背景和培训。学生将参与该项目的各个方面，从进行实验到在大学活动以及其他区域和国家会议上介绍研究结果。 学生还将有机会参加社区活动，如与神经科学学会的大脑意识周相关的活动。 这些活动让学生与公众互动，教育孩子和家长了解他们的大脑如何运作的重要性。