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.

项目摘要 杂种优势，也被称为杂种优势，是指杂种的身高，生物量和生育力的增加， 上级于父母一方或双方。杂种优势是一种基本的生物学现象， 影响农业、粮食安全和人类健康。杂种优势通常在开花植物中观察到， 包括人类在内的其他有性生殖生物。尽管它的科学意义和经济价值 重要性，杂种优势的分子基础知之甚少。最近的一项突破性发现 改变了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。在人类中，扰乱昼夜节律会导致喷气腿，疾病和生理 紊乱一个关键的问题仍然存在：杂交体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？几项研究结果使我们着手解决这一问题。首先，有一个父母- 起源影响改变昼夜基因表达和杂种优势的胚胎，这类似于一个经典的 印记的表观遗传现象。其次，与这一概念一致，染色质修饰和RNA- 定向或从头DNA甲基化介导起源亲本效应。第三，生物钟调节器， 组蛋白脱乙酰酶在同一复合物中发现，支持染色质和 昼夜节律调节。该项目的一个长期目标是确定改进工作的机制和程序， 昼夜节律和杂种优势。为此，设计实验以确定是否从头和/或 维持DNA甲基化是调节等位基因表达和杂种优势的必要和充分条件 如果母体遗传的小干扰RNA移动来调节胚胎中的空间基因表达。 值得注意的是，父母的起源效果是混淆的印记在细胞核和母亲的影响， 细胞质这些混杂效应将使用新开发的同基因胞质- 核置换系（CNS）;每对含有相同的细胞质和不同的细胞核，反之亦然。的 CNS系将被用于制造不同的杂交组合，以鉴定受印记影响的基因 或母性效应。在机制层面，有证据表明生物钟调节因子与染色质相互作用 因素将采用遗传和生物化学方法来确定DNA甲基化和 染色质因子被整合到调节杂种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新的染色质因子，并阐明其功能。结果 从这些综合的方法将提供新的和机械的见解，建立混合 胚胎活力。昼夜节律的发育和表观遗传调节原则，印记， 母体效应直接或间接关系到动物的生长发育和人类的健康。