Developmental and Epigenetic Regulation of Hybrid Vigor

项目摘要 杂种优势，也被称为杂种优势，指的是杂种的身高、生物量和育性的增加 比父母中的一方或双方优越的。杂交活力是一种基本的生物学现象，它具有翻译 对农业、粮食安全和人类健康的影响。在开花植物中通常观察到杂种优势和 包括人类在内的其他有性繁殖生物。尽管它具有科学意义和经济价值 重要的是，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 拟南芥杂交种和异源多倍体生长活力的昼夜节律变化。昼夜节律的改变 杂交种的调控增加了昼夜节律介导的能量和新陈代谢基因的表达， 增强增长活力。在人类中，扰乱昼夜节律会导致喷气腿、疾病和生理性 精神错乱。一个关键问题仍然是：杂交种中的基因组混合物如何以及何时改变基因 表情和成长活力？几个发现引导我们解决了这个问题。首先，有一位家长- 起源对胚胎昼夜节律基因表达和杂交活力的影响，这类似于经典的 印记表观遗传现象。第二，与概念一致，染色质修饰和RNA- 直接的或从头开始的DNA甲基化介导了亲本起源效应。第三，生物钟调节器和 在同一复合体中发现了一个组蛋白脱乙酰基酶，支持染色质和 昼夜节律。该项目的一个长期目标是确定改进的机制和过程 昼夜节律与杂种优势。为此，设计了实验以确定从头开始和/或 维持DNA甲基化是调节等位基因表达和杂交优势的必要条件和充分条件 如果是母系遗传的，小干扰RNA会移动来调节胚胎中的空间基因表达。 值得注意的是，母本效应是混淆的印记在细胞核和母体效应在 细胞质。这些混杂效应将利用新开发的等基因细胞质- 核代换系(CNS)；每对都含有相同的细胞质和不同的核，反之亦然。这个 CNS系将被用来制造不同的杂交组合，以识别受印记影响的基因 或母性效应。在机制层面上，有证据表明时钟调节器与染色质相互作用 各种因素。将使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的染色质因子，并将阐明它们的功能。结果 从这些综合的方法将提供新的和机械的见解，以建立混合 胚胎的活力。昼夜节律的发育和表观遗传调节的原理，印记， 母体效应将直接或间接关系到动物的发育和人类的健康。

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.