Developmental regulation of estrogen receptor-alpha by epigenetic modification

点击翻译按钮获取中文摘要

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.