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.

项目摘要/摘要该学术研究增强奖（区域）R15项目的主要目标是确定环境和遗传学的组合作用，用于基因体甲基化。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影响表达基因组并起作用。基因组表达区域的甲基化最近出现了作为一系列人类健康问题（包括癌症易感性）的信息性基因组标志物代谢疾病，神经功能和衰老。胞嘧啶的基因组分布和潜在功能无脊椎动物中的甲基化已通过研究非嗜嗜钾昆虫和海洋无脊椎动物的研究加速了包括模型cnidarian nematostella vectensis。无脊椎动物的结果强烈表明甲基化的分布高度集中在基因体（内含子和外显子）中；一个观察结果关于甲基化功能在生理和环境适应性中的功能的转化假设。先前的研究提供了甲基化景观的快照，这为对特定生理的响应基因体甲基化的动力学和机制的研究压力源，几代人以及在环境变化的长期内。 Nematostella是一个强大的解决甲基化作用的假设，原因是其配对的实用程序是实验性处理的模型具有基因组的实验室模型以及基因体甲基化和遗传的良好特征分布人口关系。拟议的研究结合了一组综合研究，以表征表观基因组调节的能力及其对非生物和生物应激源的响应的功能作用生理和分子与基因体甲基化的适应（AIM 1），从经验上确定后代中甲基化状态的遗传和DNA甲基转移酶的特定功能（AIM 2），和利用现有知识来确定自然环境的DNA甲基化的种群结构（目标3）。总之，结果将改善对动物基因体甲基化动力学的理解，不同类型的生理压力源与相对的甲基化的常见和独特的转变对后代的表观遗传修饰的跨代遗传的重要性与父母的环境。