Epigenome Dynamics During DNA Replication

DNA 复制过程中的表观基因组动力学

• 批准号: 1025830
• 负责人: Linda Hanley-Bowdoin
• 金额: $ 678.16万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1025830&HistoricalAwards=false
• 关键词: Epigenome; Dynamics; During; DNA; Replication

PI: William F. Thompson (North Carolina State University)CoPIs: George C. Allen and Linda Hanley-Bowdoin (North Carolina State University), Robert Martienssen (Cold Spring Harbor Laboratory) and Matthew W. Vaughn (University of Texas at Austin, the Texas Advanced Computing Center). Senior Personnel: Pete E. Pascuzzi (North Carolina State University) and David A. Micklos (Cold Spring Harbor Laboratory)Epigenetics, the study of structural or chemical modifications of chromosomes that affect how genetic traits are expressed, is an exciting new area of biology. However, very little is yet known about the processes that transmit these structural or chemical modifications - known as "epigenetic marks" - through the multiple rounds of DNA replication and cell division that are required to make a plant or animal. Understanding this cell-to-cell transmission requires understanding events occurring only during the small part of the cell cycle in which DNA is synthesized ("S-phase"). In this project, the tools and knowledge from a previous NSF-supported project will be used to study transmission of epigenetic marks through S phase in two important model systems - maize and Arabidopsis. The results are expected to be relevant to most plants and animals. Millions of plant cell nuclei will be isolated and then sorted into groups depending on how much DNA they contain using a technique called flow cytometry . This sorting technique will provide material for a genome-wide analysis of epigenetic marks at each of several stages in the DNA replication process. Studying the sequence of events through the replication cycle will help to understand the molecular mechanisms that lead to formation active or inactive structures at different places along a chromosome. Similar techniques applied to mutant plants with known defects in chromosome structure or function may help highlight even more subtle control mechanisms. The results are expected to provide a better understanding of how genes are affected by structural and chemical modifications of DNA and the chromosomes in which it is housed. Understanding these epigenetic influences will have a profound impact on both basic and applied plant biology. For example, many crops are propagated clonally, and the occasional occurrence of "sports" (epigenetic variants) can impact both yield and quality. Another example involves crops engineered by gene transfer, which often experience unexpected inactivation, or "silencing", of the transferred gene. Silencing greatly complicates the process of obtaining commercially viable plant lines. This project will contribute to the ability to predict, and perhaps to control, gene silencing, which will be of considerable value for a wide variety of applications.The project will bring together investigators with expertise in biochemistry, molecular biology, genetics, genomics and bioinformatics, and support a productive collaboration between two major research institutions. An excellent training environment for graduate and postdoctoral students will be provided, and selected undergraduates will participate in various aspects of the research. There will be two principal outreach efforts. A successful "Science in a Suitcase" unit on Genetics for middle schools, created during a previous PGRP project, will be updated, and teacher workshops will be extended to include many more teachers and students. In addition, a program in epigenetics will be inaugurated at the Dolan DNA Learning Center. This program will target advanced high school students and faculty at two year and agricultural colleges, and will provide valuable resources for teaching about epigenetics. A combination of web materials and podcasts, as well as resources for experiments, will be created. Public access to information about this project, including links to primary data, will be provided through the project website (www.plantreplication.net), GEO (http://www.ncbi.nlm.nih.gov/geo/), the NCBI's SRA (http://www.ncbi.nlm.nih.gov/sra), Gramene (http://www.gramene.org/), MaizeGDB (http://www.maizegdb.org/), and TAIR (http://www.arabidopsis.org/).

PI：威廉·汤普森（William F. Thompson）（北卡罗来纳州立大学）COPIS：乔治·C·艾伦（George C. 高级人员：Pete E. Pascuzzi（北卡罗来纳州立大学）和David A. Micklos（冷泉港实验室）表观遗传学，研究染色体的结构或化学修饰的研究，这些染色体影响遗传特征的表达方式，是一种令人兴奋的新生物学领域。然而，关于通过多个植物或动物所需的DNA复制和细胞分裂传播这些结构或化学修饰的过程（称为“表观遗传标记”）的过程鲜为人知。了解这种细胞向细胞的传播需要了解仅在合成DNA的细胞周期的一小部分中发生的事件（“ S相”）。在该项目中，以前的NSF支持项目的工具和知识将用于研究两个重要模型系统（玉米和拟南芥）中S阶段的表观遗传标记的传播。结果预计将与大多数动植物有关。将分离数百万个植物细胞核，然后根据使用一种称为流式细胞仪的技术所包含的DNA进行分离，并将其分为组。这种排序技术将为DNA复制过程中每个阶段的每个阶段的表观遗传标记进行全基因组分析提供材料。通过复制周期研究事件的序列将有助于理解导致沿染色体不同位置的活性或非活性结构的分子机制。应用于染色体结构或功能中已知缺陷的突变植物的类似技术可能有助于突出更微妙的控制机制。预计该结果将更好地了解基因如何受到DNA的结构和化学修饰的影响以及其所容纳的染色体。了解这些表观遗传影响将对基本和应用植物生物学产生深远的影响。例如，许多农作物是在克隆的繁殖中，偶尔出现“运动”（表观遗传变体）会影响产量和质量。另一个例子涉及通过基因转移设计的作物，这些农作物通常会经历转移的基因的意外失活或“沉默”。沉默非常复杂，获得商业上可行的植物线的过程。该项目将有助于预测和控制基因沉默的能力，这对于各种应用将具有相当大的价值。该项目将把研究人员聚集在生物化学，分子生物学，遗传学，基因组学和生物信息学方面的专业知识，并支持两个主要研究机构之间的有效协作。将为研究生和博士后学生提供出色的培训环境，而精选的本科生将参与研究的各个方面。将有两项主要的宣传工作。在上一项PGRP项目期间创建的中学遗传学的成功的“手提箱中的科学”将被更新，并将扩展教师研讨会，包括更多的教师和学生。此外，在多兰DNA学习中心将开设表观遗传学的计划。该计划将针对两年的高级高中生和教职员工，并将为农业学院提供，并为有关表观遗传学的教学提供宝贵的资源。将创建网络材料和播客以及实验资源的结合。 Public access to information about this project, including links to primary data, will be provided through the project website (www.plantreplication.net), GEO (http://www.ncbi.nlm.nih.gov/geo/), the NCBI's SRA (http://www.ncbi.nlm.nih.gov/sra), Gramene （http://www.gramene.org/），maizegdb（http://www.maizegdb.org/）和Tair（http://www.arabidopsis.org/）。