RUI: Analysis of Epigenetic Modifications Regulating Genomic Imprinting in Mouse

智力优点：哺乳动物中的大多数基因都是从母亲和父亲遗传的拷贝中表达的，但少数基因只从两个拷贝中的一个表达-这些被称为印记基因。两个亲本拷贝的印记基因必须通过印记标记彼此区分，以适当地控制它们的表达。对于某些基因，印迹标记已被证明是由DNA和/或DNA包裹在细胞中的蛋白质的修饰组成;这种修饰被称为表观遗传，因为它们影响DNA和染色质结构，但不影响DNA序列。本研究旨在研究哺乳动物发育过程中表观遗传修饰的获得，以更好地了解染色体结构如何影响印记基因的表达。解决这个问题的一种方法是通过研究在小鼠胚胎发育的不同阶段特定印记基因处的DNA甲基化的获得。然后将获得的数据与相邻基因处的DNA甲基化获取模式进行比较，以检验染色质结构的修饰在基因组的相邻区域中受到协调控制的假设。此外，本研究还将研究经修饰的组蛋白在印迹Rasgrf 1基因上的分布。Rasgrf 1在某些组织中仅从父系拷贝表达，但在其他组织中从两个拷贝表达。由于DNA甲基化仅与Rasgrf 1的父系拷贝相关，因此其他表观遗传因素必须负责调节该基因的组织特异性印记。总体而言，这项研究将提供深入了解的机制，建立和维护的染色质结构的关键印记gene expression.Broader影响：这项工作将在布林莫尔学院，一个全女性的本科院校，具有杰出的记录，培养年轻的女科学家进行。本科生将参与的主要研究人员，并将学习在夏季和学年期间PI的直接监督和指导下进行和批判性地评估科学研究。参与该项目的学生将在表观遗传学和基因组印记的新兴领域进行前沿研究，通过使用当前的方法来推进科学探索，从而改善教育环境。在实验室进行研究的学生将参加每周的实验室会议，每年向学院社区展示他们的研究成果，并通过在同行评审的期刊上发表和在国际科学会议和本科生研究研讨会上发表演讲，将他们的数据传播给更广泛的科学界。所有这些与研究相关的活动将为学生在生物科学领域的进一步教育或职业生涯做好准备。

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.