RUI: Analysis of Epigenetic Modifications Regulating Genomic Imprinting in Mouse

智力优势：哺乳动物中的大多数基因都是从母亲和父亲那里继承的副本中表达的，但也有一小部分基因只在两个副本中的一个副本中表达--这些基因被称为印记基因。印记基因的两个双亲拷贝必须通过印记标记彼此区分，以便适当地控制它们的表达。对于一些基因，印记标记已被证明包括对DNA和/或DNA在细胞中包裹的蛋白质的修改；这种修改被称为表观遗传，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，以便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的DNA甲基化的获得。然后将获得的数据与邻近基因的DNA甲基化获取模式进行比较，以验证染色质结构的修改在基因组的相邻区域之间受到协调控制的假设。此外，这项研究还将检测印迹Rasgrf1基因上修饰的组蛋白的分布。Rasgrf1在某些组织中只在父系拷贝中表达，但在其他组织中两个拷贝都表达。因为DNA甲基化只与Rasgrf1的父系拷贝有关，所以额外的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，这项研究将有助于深入了解对印记基因表达至关重要的染色质结构的建立和维持机制。广泛影响：这项工作将在布林·莫尔学院进行，这是一所全女性本科生机构，在培养年轻女性科学家方面有着出色的记录。本科生将是主要的研究人员，在暑假和学年期间，他们将学习在PI的直接监督和指导下进行科学研究并对其进行批判性评估。参与这个项目的学生将在表观遗传学和基因组印迹等新兴领域进行尖端研究，通过使用当前的方法来促进科学探索，从而改善教育环境。在实验室进行研究的学生将参加每周一次的实验室会议，每年向学院社区展示他们的研究成果，并通过在同行评议的期刊上发表文章以及在国际科学会议和本科生研究座谈会上发表演讲，向更广泛的科学界传播他们的数据。所有这些与研究相关的活动都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.