Environmental and Genetic Determinants of Dynamics in Gene Body Methylation

项目摘要/摘要 这个学术研究促进奖(AREA)R15项目的主要目标是确定 环境和遗传学在基因体甲基化中的组合作用。表观遗传学表观遗传学的研究，尤指 甲基化，强调了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。 作为人类一系列健康问题的信息性基因组标记，包括癌症易感性， 代谢性疾病、神经功能和衰老。胞嘧啶的基因组分布及其潜在功能 通过对非果蝇类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， 包括线虫线虫模型。无脊椎动物的研究结果强烈表明， 甲基化的分布高度集中在基因体(内含子和外显子)；这一观察到 改变了有关甲基化在生理学和环境适应中的作用的假设。 以前的研究已经提供了甲基化环境的快照，这为 特定生理条件下基因体甲基化的动态及机制研究 压力源，跨越几代人，以及较长时间的环境变化。线虫是一种强大的 模型来解决甲基化作用的假设，因为它是一种实验上容易处理的配对实用程序， 基因组使能的实验室模式和基因体甲基化和基因的良好分布 种群间的关系。拟议的研究结合了一系列综合研究，以表征 表观基因组调节能力及其在响应非生物和生物应激源连接中的功能作用 基因体甲基化的生理和分子习服(目标1)，经验性地决定了 子代甲基化状态的遗传和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DNA甲基化的种群结构 (目标3)。总之，这些结果将提高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共同和独特的变化，以及相对的 表观遗传修饰的跨代遗传对后代遭遇共享的重要性 有父母的环境。

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.