Developmental and Epigenetic Regulation of Hybrid Vigor

杂种活力的发育和表观遗传调控

• 批准号: 9240315
• 负责人: ZENGJIAN JEFFREY CHEN
• 金额: $ 31.73万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-08 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9240315
• 关键词: Address; Agriculture; Alleles; Angiosperms; Animals; Arabidopsis; Backcrossings; Binding; Biochemical; Biological Assay; Biological Phenomena; Biomass; CRISPR/Cas technology; Cell Nucleus; ChIP-seq; Chromatin; Circadian Rhythms; Clock protein; Complex; Conflict (Psychology); Cytoplasm; DNA Maintenance; DNA Methylation; Development; Disease; Economics; Embryo; Embryonic Development; Energy Metabolism; Epigenetic Process; Fertility; Gene Expression; Gene Targeting; Generations; Genes; Genetic; Genetic Transcription; Genomic approach; Genomics; Goals; Growth; HDAC4 gene; Health; Human; Hybrid Vigor; Hybrids; Inherited; Leg; Link; Mediating; Metabolic Diseases; Methylation; Modeling; Molecular; Nuclear; Organism; Output; Parents; Pathway interactions; Phase; Physiological; Plants; Process; Proteomics; RNA; Recruitment Activity; Regulation; Reporter; Role; Small Interfering RNA; Testing; animal breeding; base; chromatin modification; circadian pacemaker; design; epigenetic regulation; experimental study; food security; genetic approach; genomic tools; imprint; improved; innovation; insight; male; mutant; novel; overexpression; paternal imprint; protein complex; translational impact

Project Summary Hybrid vigor, also known as heterosis, refers to the increase in stature, biomass, and fertility of a hybrid that is superior to one or both parents. Hybrid vigor is a fundamental biological phenomenon that has translational impact on agriculture, food security, and human health. Heterosis is commonly observed in flowering plants and other sexually reproducing organisms including humans. In spite of its scientific significance and economic importance, molecular bases for heterosis are poorly understood. A recent breakthrough finding has linked altered circadian rhythms to growth vigor in Arabidopsis hybrids and allopolyploids. The altered circadian regulation in the hybrids increases expression of circadian-mediated genes in energy and metabolism, promoting growth vigor. In humans, disrupting circadian rhythms causes jet leg, diseases and physiological disorders. A key question remains: how and when does the genomic mixture in the hybrids alter gene expression and growth vigor? Several findings have led us to address this question. First, there is a parent-of- origin effect on altered circadian gene expression and hybrid vigor in embryos, which resembles a classical epigenetic phenomenon of imprinting. Second, consistent with the notion, chromatin modifications and RNA- directed or de novo DNA methylation mediate the parent-of-origin effect. Third, a circadian clock regulator and a histone deacetylase are found in the same complex, supporting an interactive role between chromatin and circadian regulation. A long-term goal of the project is to define mechanisms and processes for improving circadian rhythms and heterosis. Towards this end, experiments are designed to determine if de novo and/or maintenance DNA methylation is necessary and sufficient to regulate allelic gene expression and hybrid vigor and if maternally inherited small interfering RNAs move to regulate spatial gene expression in the embryo. Notably, the parent-of-origin effect is confounded by imprinting in nuclei and by maternal effect in the cytoplasm. These confounding effects will be discriminated using newly developed isogenic cytoplasmic- nuclear substitution lines (CNS); each pair contains the same cytoplasm and different nuclei or vice versa. The CNS lines will be used to make different hybrid combinations to identify the genes that are subject to imprinting or maternal effect. At the mechanistic level, there is evidence that clock regulators interact with chromatin factors. Genetic and biochemical approaches will be employed to determine how DNA methylation and chromatin factors are integrated into the circadian pathway that regulates hybrid vigor. Proteomic approaches will be used to identify new chromatin factors in hybrid embryos, and their functions will be elucidated. Results from these integrated approaches will provide new and mechanistic insights into the establishment of hybrid vigor in embryos. The principles for developmental and epigenetic regulation of circadian rhythms, imprinting, and maternal effect will be directly or indirectly relevant to animal development and human health.

项目概要 杂种优势，也称为杂种优势，是指杂种的身材、生物量和育性的增加 优于父母一方或双方。混合活力是一种基本的生物现象，具有转化性 对农业、粮食安全和人类健康的影响。杂种优势常见于开花植物中 其他有性生殖生物，包括人类。尽管其具有科学意义和经济意义 尽管杂种优势的分子基础非常重要，但人们对杂种优势的分子基础知之甚少。最近的一项突破性发现将 改变拟南芥杂种和异源多倍体的生长活力的昼夜节律。改变的昼夜节律 杂种中的调节增加了能量和代谢中昼夜节律介导的基因的表达， 促进生长活力。对于人类来说，扰乱昼夜节律会导致时差、疾病和生理问题 失调。一个关键问题仍然存在：杂交种中的基因组混合物如何以及何时改变基因 表达和生长活力？多项发现引导我们解决这个问题。首先，有一个父母—— 起源对胚胎中昼夜节律基因表达和杂交活力改变的影响，类似于经典的 印记的表观遗传现象。其次，与这个概念一致，染色质修饰和RNA- 定向或从头 DNA 甲基化介导亲本效应。第三，生物钟调节器和 在同一复合物中发现了组蛋白脱乙酰酶，支持染色质和 昼夜节律调节。该项目的长期目标是定义改进机制和流程 昼夜节律和杂种优势。为此，设计实验以确定是否从头开始和/或 维持 DNA 甲基化对于调节等位基因表达和杂交活力是必要且充分的 母系遗传的小干扰RNA是否能够调节胚胎中的空间基因表达。 值得注意的是，亲本效应被细胞核中的印记和母体效应所混淆。 细胞质。这些混杂效应将使用新开发的同基因细胞质来区分 核替代系（CNS）；每对包含相同的细胞质和不同的细胞核，反之亦然。这 CNS系将用于制作不同的杂交组合，以识别受到印记的基因 或母体效应。在机制层面，有证据表明时钟调节器与染色质相互作用 因素。将采用遗传和生化方法来确定 DNA 甲基化和 染色质因子被整合到调节杂交活力的昼夜节律途径中。蛋白质组学方法 将用于鉴定杂交胚胎中的新染色质因子，并阐明它们的功能。结果 这些综合方法将为混合动力的建立提供新的、机械的见解 胚胎的活力。昼夜节律的发育和表观遗传调节原理、印记、 母体效应将直接或间接与动物发育和人类健康相关。