RUI: Analysis of Epigenetic Modifications Regulating Genomic Imprinting in Mouse

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Intellectual merit: The majority of genes in mammals are expressed from copies inherited from both the mother and the father, but a small number of genes are only expressed from one of the two copies - these are called imprinted genes. The two parental copies of imprinted genes must be distinguished from each other via an imprinting mark in order to properly control their expression. For some genes, the imprinting mark has been shown to consist of modifications to the DNA and/or to the proteins DNA wraps around in the cell; such modifications are called epigenetic because they affect DNA and chromatin structure but not DNA sequence. This research aims to investigate the acquisition of epigenetic modifications during mammalian development in order to better understand how chromosome structure influences the expression of imprinted genes. One way of addressing this question is by investigating the acquisition of DNA methylation at a specific imprinted gene at different stages of mouse embryonic development. The data obtained will then be compared to the pattern of DNA methylation acquisition at an adjacent gene in order to test the hypothesis that modifications to chromatin structure are coordinately controlled across neighboring regions of the genome. In addition, this research will examine the distribution of modified histone proteins at the imprinted Rasgrf1 gene. Rasgrf1 is expressed solely from the paternal copy in some tissues, but is expressed from both copies in other tissues. Because DNA methylation is associated only with the paternal copy of Rasgrf1, additional epigenetic factors must be responsible for regulating tissue-specific imprinting of this gene. Overall, this research will lend insight into the mechanisms governing the establishment and maintenance of chromatin structure critical for imprinted gene expression.Broader Impacts: This work will be conducted at Bryn Mawr College, an all-female undergraduate institution with an outstanding record of training young women scientists. Undergraduate students will be the primary researchers involved and will learn to conduct and critically evaluate scientific research under the direct supervision and mentorship of the PI during both the summer and the academic year. Students involved in this project will conduct cutting-edge research in the emerging fields of epigenetics and genomic imprinting, leading to an enhanced educational environment through the use of current methodologies to advance scientific exploration. Students conducting research in the lab will attend weekly lab meetings, present their research to the College community annually, and disseminate their data to the broader scientific community through publication in peer-reviewed journals and presentations at both international scientific conferences and undergraduate research symposia. All of these research-related activities will prepare students for further education or careers in the biological sciences.