Environmental and Genetic Determinants of Dynamics in Gene Body Methylation

基因体甲基化动态的环境和遗传决定因素

基本信息

批准号：
10569379
负责人：
Adam Michael Reitzel
金额：
$ 11.03万
依托单位：
UNIVERSITY OF NORTH CAROLINA CHARLOTTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2024-05-31
项目状态：
已结题

项目摘要

PROJECT SUMMARY/ABSTRACT The major objective of this Academic Research Enhancement Award (AREA) R15 project is to determine the combinatory roles for environment and genetics for gene body methylation. The study of epigenetics, particularly methylation, has emphasized that chemical and physical modifications of DNA can profoundly influence how the genome is expressed and functions. The methylation of expressed regions of the genome has recently emerged as an informative genomic marker for a range of human health concerns, including cancer susceptibility, metabolic diseases, neurological function, and aging. The genomic distribution and potential function of cytosine methylation in invertebrates has accelerated through studies of non-drosophilid insects and marine invertebrates, including the model cnidarian Nematostella vectensis. Results from invertebrates strongly suggest that the distribution of methylation is highly concentrated in gene bodies (introns and exons); an observation that has transformed hypotheses about the function of methylation in physiology and environmental acclimatization. Previous research has provided snap-shots of the methylation landscape that has opened opportunities for studies of the dynamics and mechanisms of gene body methylation in response to specific physiological stressors, across generations, and over extended periods of environmental variation. Nematostella is a powerful model to address hypotheses for the roles of methylation due to its paired utility as an experimentally tractable, genome-enabled lab model and the well-characterized distribution of gene body methylation and genetic relationships of populations. The proposed research combines an integrated set of studies to characterize the capacity for epigenome regulation and its functional role in response to abiotic and biotic stressors to connect physiological and molecular acclimatization with gene body methylation (Aim 1), empirically determine the inheritance of methylation states in offspring and the specific functions for DNA methyltransferases (Aim 2), and leverage existing knowledge to determine the population structure of DNA methylation of natural environments (Aim 3). Together, the results will improve understanding of the dynamics of gene body methylation in animals, the common and unique shifts in methylation between different types of physiological stressors, and relative importance of transgenerational inheritance of epigenetic modifications for offspring encountering shared environments with parents.

项目概要/摘要该学术研究增强奖 (AREA) R15 项目的主要目标是确定环境和遗传学对基因体甲基化的组合作用。表观遗传学的研究，特别是甲基化，强调 DNA 的化学和物理修饰可以深刻地影响基因组的表达和功能。最近出现了基因组表达区域的甲基化作为一系列人类健康问题（包括癌症易感性）的信息基因组标记，代谢疾病、神经功能和衰老。胞嘧啶的基因组分布和潜在功能通过对非果蝇昆虫和海洋无脊椎动物的研究，无脊椎动物的甲基化加速了，包括模式刺胞动物 Nematostella vectensis。无脊椎动物的结果强烈表明甲基化分布高度集中在基因体（内含子和外显子）；一个观察结果改变了关于甲基化在生理学和环境适应中的功能的假设。先前的研究提供了甲基化景观的快照，这为研究基因体甲基化响应特定生理的动力学和机制压力源，跨代，以及长期的环境变化。线虫是一种强大的模型来解决甲基化作用的假设，因为它作为实验上易于处理的配对效用，基因组支持的实验室模型以及基因体甲基化和遗传特征的分布人群的关系。拟议的研究结合了一组综合研究来描述表观基因组调节能力及其在响应非生物和生物应激源方面的功能作用基因体甲基化的生理和分子适应（目标 1），凭经验确定后代甲基化状态的遗传以及 DNA 甲基转移酶的特定功能（目标 2），以及利用现有知识确定自然环境中 DNA 甲基化的群体结构（目标 3）。总之，这些结果将增进对动物基因体甲基化动态的理解，不同类型的生理应激源之间甲基化的常见和独特的变化以及相对表观遗传修饰的跨代遗传对于后代遇到共享的重要性和父母一起的环境。