The Mechanism and Function of SDG2 in Regulating Chromatin Structure and Gene Expression

智力优势：在真核细胞中，DNA通过包裹在组蛋白八聚体周围而包装成染色质。许多发生在染色质水平上的分子过程都受到染色质结构性质的深刻影响。近年来的大量工作证实了组蛋白翻译后修饰的重要性，如赖氨酸残基的甲基化，在调节染色质结构和基因表达方面。拟南芥中的SDG2蛋白是一个未知的高度保守的赖氨酸甲基转移酶家族的成员。功能丧失的sdg2突变植株表现出许多发育异常和数百个基因的错误调控，以及特定基因上的组蛋白甲基化缺陷。这些结果表明，SDG2在调控基因表达和植物发育方面起着至关重要的作用。本课题旨在阐明SDG2的作用机制和功能。第一个目的是通过全基因组鉴定直接受SDG2调控的基因以及SDG2缺失引起的组蛋白甲基化缺陷来了解SDG2的功能。第二个目的是通过确定SDG2的酶和底物特异性来了解SDG2修饰组蛋白的机制。第三个目标是通过分离与SDG2相互作用的蛋白质，了解SDG2在发育过程中是如何针对特定基因的。这些研究有望揭示SDG2的机制和功能。此外，考虑到不同组蛋白修饰途径之间复杂而密切的相互作用，该项目的结果也有望有助于更广泛地理解组蛋白修饰的机制和功能。广泛的影响：该项目的更广泛的影响是几个方面的。这项研究是多学科的，因此非常适合培养未来的科学家，包括本科生研究助理、研究生和博士后研究助理。该项目还将对教学产生立竿见影的积极影响。PI教授植物遗传学和分子生物学的系列讲座，重点是使用基因组方法来研究复杂的生物过程。本课程将从构思的想法和从这个项目中获得的知识中获益良多。此外，国际科学协会将积极参与两个旨在通过加强现有和未来中学科学教师的课堂和动手培训来促进K-12科学教育的方案。PI将为未来的中学科学教师(当前教育专业的学生)开发一门本科课程，重点是注入热情和激发科学教师的好奇心，并将在未来传递给中学生。此外，国际教师联合会将通过资助现有教师进行暑期研究，参加佐治亚州实习生教师奖学金(GIFT)。该项目旨在提高教师的批判性思维和解决问题的能力，并帮助他们将现实世界的科学研究和应用与他们在课堂上教授的“教科书科学”联系起来。

Intellectual Merit: In eukaryotic cells, DNA is packaged into chromatin by wrapping around histone octamers. Many molecular processes that take place at the chromatin level are profoundly affected by the structural properties of the chromatin. A large body of work in recent years has established the importance of post-translational modifications of histones, such as methylation of lysine residues, in modulating chromatin structure and gene expression. The SDG2 protein in Arabidopsis thaliana is a member of a previously uncharacterized and highly conserved lineage of putative lysine methyltransferases. Loss-of-function sdg2 mutant plants exhibit numerous developmental abnormalities and the mis-regulation of hundreds of genes, as well as histone methylation defects at specific loci. These results indicate that SDG2 is critically important in regulating gene expression and plant development. This project is directed to elucidate the mechanism of action and function of SDG2. The first aim is to understand the function of SDG2 by genome-wide identification of the genes that are directly regulated by SDG2 and the histone methylation defects caused by the loss of SDG2. The second aim is to understand the mechanism by which SDG2 modifies histones by determining its enzymatic and substrate specificities. The third aim is to understand how SDG2 is targeted to specific genes during development by isolating proteins that interact with SDG2. These studies are expected to reveal significant insights into the mechanisms and functions of SDG2. In addition, considering the complex and intimate interactions among different histone modification pathways, the results from this project are also expected to assist in the broader understanding of the mechanisms and functions of histone modifications.Broader Impacts: The broader impacts of this project are several fold. The research is multi-disciplinary in nature and therefore ideally suited for training future scientists, including undergraduate research assistants, a graduate student and a postdoctoral research associate. This project will also have an immediate and positive impact on teaching. The PI teaches a lecture series on plant genetics and molecular biology, with emphasis on the use of genomic approaches to study complex biological processes. This course should benefit tremendously from the ideas conceived and the knowledge gained from this project. In addition, the PI will be actively engaged in two programs designed to promote K-12 science education by enhancing the classroom and hands-on training of current and future middle school science teachers. The PI will develop an undergraduate course for future middle school science teachers (current education major students) with a particular emphasis on injecting enthusiasms into and stimulating the curiosities of science teachers, which will be relayed to middle school students in the future. Also, the PI will participate in the Georgia Intern-Fellowships for Teachers (GIFT) by sponsoring current teachers for summer research. This program is expected to improve the critical thinking and problem solving abilities of the teachers, and to help them connect real-world scientific research and application with the "textbook science" that they teach in the classroom.