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

项目摘要 表观遗传修饰是一种重要的基因调控机制， 基因组完整性、发育、环境反应和疾病的控制。尽管 大量的研究描述了异常发育和发育过程中改变的修饰模式， 病理组织，无论它们是原因还是结果，都知之甚少。这项建议 剖析了表观遗传调控的分子机制，以及改变了的表观遗传调控的功能后果。 生理条件下的表观遗传模式。具体来说，我们研究1）染色质如何 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; 3）表观遗传修饰如何保护基因组完整性。 我们使用开花植物拟南芥，被证明是一个强大的机制表观遗传 学习，作为我们的模型系统。拟南芥和哺乳动物有共同的核心胞嘧啶DNA 其它模式生物（例如酿酒酵母， 秀丽隐杆线虫和黑腹果蝇）。重要的是，拟南芥容忍空 大多数表观遗传调节因子的突变通常在动物中是致命的，这提供了一个重要的 有利于深入研究发育和生理条件下的机制。作为 我们探索了真核生物中保守的表观遗传调控的基本原则， 生物，从我们在拟南芥的开创性研究中获得的知识将有助于加速 在破译人类相关机制方面取得了进展。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至关重要， 疾病这些知识将提供必要的洞察力，以开发新的药物， 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.