Epigenetic Inheritance of Physiological Phenotypes: Occurrence, Mechanism and Inter-and Intra-individual Variation

生理表型的表观遗传：发生、机制以及个体间和个体内变异

• 批准号: 1543301
• 负责人: Warren Burggren
• 金额: $ 30万
• 依托单位: University of North Texas
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1543301&HistoricalAwards=false
• 关键词: Epigenetic; Inheritance; Physiological; Phenotypes; Occurrence

The exact set of traits and features possessed by an animal (phenotypes) is shaped by genetic factors provided by maternal and paternal contributions to the genome. The phenotypes are also shaped by so-called "epi-genetic" changes that impact gene expression but do not change the sequence of the DNA. This award supports a two year EAGER project that focuses on the unexplored epigenetic inheritance of modified phenotypes of a higher-order physiological process, cardiovascular performance, and how physiological variation might result from mechanistic variation. Among key novel aspects of the proposed experiments is the focus on "true" transgenerational epigenetic inheritance in non-placental animals, rather than in utero or maternal effects. This project will focus on inter- and intra-individual variation in the underlying molecular mechanisms. The significant Broader Impacts of this proposal include the cross-training of a cohort of both US students and Mexican graduate students (involving UNT's new agreement with Mexico's CONACyT funding agency). These students will receive training in the nexus of physiology and epigenetics as well as an enriched perspective on international research coordination.Three hypotheses will be tested in the course of this project: H1: The Transgenerational Epigenetic Effect. Exposure to aquatic hypoxia in mature adult zebrafish (P0) before they begin reproduction will modify cardiovascular phenotype in their offspring (F1 and possibly F2 and beyond); H2: Epigenetic Dynamics. Epigenetically-inherited cardiovascular phenotypes are highly dynamic, showing both variation between individuals and slowly disappearing (fading out) across generations; and H3: Epigenetic Mechanisms. The germ-line of the P0 generation experiences variable degrees of DNA methylation and/or histone modification that lingers through subsequent fertilization and development, which may be correlated with variably altered gene expression and hence variation in the modified physiological phenotypes in the F1 generation. Data from this study are likely to underscore an emerging yet still vaguely defined rationale for why epigenetic inheritance has been selected for as a mechanism for surviving environmental changes that span several generations. Results will be disseminated through publication in peer-reviewed journals and through presentation at scientific meetings.

动物所具有的确切的性状和特征集（表型）是由母系和父系对基因组的贡献所提供的遗传因素形成的。 表型也由所谓的“表观遗传”变化形成，这些变化影响基因表达，但不改变DNA序列。 该奖项支持一个为期两年的EAGER项目，该项目专注于高阶生理过程的修饰表型的未探索的表观遗传，心血管性能，以及生理变异如何可能导致机械变异。在拟议的实验中，关键的新颖方面是关注非胎盘动物中“真正的”跨代表观遗传遗传，而不是子宫内或母体效应。该项目将重点关注潜在分子机制中的个体间和个体内变异。 该提案的重大影响包括美国学生和墨西哥研究生的交叉培训（涉及UNT与墨西哥国家科学技术委员会资助机构的新协议）。这些学生将接受生理学和表观遗传学的联系方面的培训，以及对国际研究协调的丰富观点。在这个项目的过程中，将测试三个假设：H1：跨代表观遗传效应。暴露于水生缺氧在成熟的成年斑马鱼（P0）之前，他们开始繁殖将修改心血管表型在他们的后代（F1和可能的F2及以后）; H2：表观遗传动力学。表观遗传的心血管表型是高度动态的，显示个体之间的变化和跨代缓慢消失（淡出）;和H3：表观遗传机制。P0代的生殖系经历了不同程度的DNA甲基化和/或组蛋白修饰，这些修饰在随后的受精和发育过程中一直存在，这可能与F1代中基因表达的改变有关，因此与生理表型的改变有关。这项研究的数据可能会强调一个新兴的，但仍然模糊定义的理由，为什么表观遗传遗传已被选定为一种机制，生存的环境变化，跨越几代人。 将通过在同行评审的期刊上发表和在科学会议上介绍的方式传播研究结果。