Uncovering the epigenetic codes for genome integrity, developmental and environmental interaction.

项目总结 表观遗传修饰是一种重要的基因调控机制，在 基因组完整性、发育、环境反应和疾病的控制。尽管 大量研究描述了发育和发育异常的改变的修改模式 病理组织，无论它们是原因还是结果，人们都知之甚少。这项建议 剖析了表观遗传调控的分子机制和改变的功能后果 生理条件下的表观遗传模式。具体地说，我们研究1)染色质是如何 感知和记忆环境刺激；2)表观遗传开关如何调节 发育阶段转变；以及3)表观遗传修饰如何保护基因组的完整性。 我们使用开花植物拟南芥，它被证明是一个强大的机械表观遗传系统 学习，作为我们的典范系统。拟南芥与哺乳动物共享共同的核心胞嘧啶DNA 甲基化机制是其他模式生物(例如酿酒酵母、 秀丽线虫和黑腹果蝇)。重要的是，拟南芥耐受Null 大多数表观遗传调节器的突变通常对动物是致命的，提供了显著的 有利于研究发育和生理条件下的深入机制。AS 我们探讨了在真核生物中保守的表观遗传调控的基本原则。 生物体，从我们对拟南芥的开创性研究中获得的知识将有助于加快 人类相关机制的破译进展。深入的机械知识是 对于理解表观遗传修饰如何导致发育缺陷和 疾病。这些知识将提供必要的洞察力来开发针对 各自的表观遗传过程。

PROJECT SUMMARY Epigenetic modification is an important gene regulatory mechanism and plays quintessential roles in the control of genome integrity, development, environmental responses, and diseases. Despite the large amount of studies describing altered modification patterns in abnormal developmental and pathological tissues, whether they are a cause or a consequence is poorly understood. This proposal dissects molecular mechanism of epigenetic regulation and functional consequences of altered epigenetic patterns under physiological conditions. Specifically, we investigate 1) how chromatin senses and memorizes the environmental stimuli; 2) how an epigenetic switch regulates developmental phase transition; and 3) how epigenetic modification safeguards the genome integrity. We use the flowering plant Arabidopsis, proved to be a robust system for mechanistic epigenetic studies, as our model system. Arabidopsis shares with mammals the common core cytosine DNA methylation machinery that is lacking in other model organisms (e.g. Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster). Importantly, Arabidopsis tolerates null mutations in most epigenetic regulators that are often lethal in animals, providing a significant advantage to investigate in-depth mechanisms under developmental and physiological conditions. As we probe basic principles governing epigenetic regulation that are conserved across eukaryotic organisms, knowledge acquired from our pioneering studies in Arabidopsis will help accelerate progress in deciphering the relevant mechanisms in human. In-depth mechanistic knowledge is crucial for understanding how epigenetic modification contributes to developmental defects and disease. Such knowledge will provide the necessary insight to develop new medicines that target the respective epigenetic processes.