Establishment and Modulation of DNA Methylation Patterns in Arabidopsis

摘要 在任何给定的有机体中，每个细胞都有基本上相同的遗传物质，但并不是所有的细胞都有相似的行为。 这种显著的多样性的一个来源是化学标签的存在，比如DNA甲基化，它装饰着 基因组在不同的生物过程中发挥作用，包括基因调控、转座子沉默和 印记。虽然众所周知，DNA甲基化的模式在组织或细胞类型之间可能不同，但如何 这种模式是产生的，它们如何影响基因表达模式仍然知之甚少。AS DNA甲基化异常模式与植物的发育缺陷有关，并与许多 对于人类疾病，理解表观遗传调控的这些方面是至关重要的。 利用植物模型拟南芥，该实验室最近发现了一个四个相关的染色质家族 以特定部位和组织的方式控制DNA甲基化模式的重塑因子。基于新的 在描述这些染色质调节器的过程中获得的洞察力，这项提案试图理解 促进DNA甲基化的位点特异性靶向的机制，以确定制衡 能够在甲基化途径中实现基因组规模的动态平衡，并研究遗传和 表观遗传输入被整合以调节DNA甲基化模式。解决表观遗传学的这些方面 调控不仅对于理解DNA甲基化在正常生长和生长过程中的作用至关重要 发展，但它们也将提供对DNA内部调控失调的原因和后果的见解 甲基化途径。 拟南芥是研究表观遗传过程的理想系统，如dna甲基化。 可塑性，有一个小的基因组，高度服从全基因组分析，并容忍戏剧性的 其表观遗传景观的变化。此外，参与建立的许多关键参与者和途径， 维持和阅读表观遗传修饰在植物和哺乳动物之间是保守的。考虑到这些 关于特定甲基化模式是如何产生和调节的相似性和发现 发展，将适用于哺乳动物的类似过程。

Abstract Within any given organism, each cell has essentially identical genetic material, yet not all cells behave similarly. One source of this remarkable diversity is the presence of chemical tags, like DNA methylation, that decorate the genome and play roles in diverse biological processes including gene regulation, transposon silencing, and imprinting. While it is known that the patterns of DNA methylation can differ between tissues or cell types, how such patterns are generated and how they influence gene expression patterns remain poorly understood. As aberrant DNA methylation patterns are associated with developmental defects in plants and with numerous diseases in humans, understanding these aspects of epigenetic regulation are of critical importance. Using the plant model, Arabidopsis thaliana, the lab recently discovered a family of four related chromatin remodeling factors that control DNA methylation patterns in a locus- and tissue-specific manner. Based on new insights gained during the characterization of these chromatin regulators, this proposal seeks to understand the mechanisms that facilitate the locus-specific targeting of DNA methylation, to determine the checks and balances that enable genome-scale homeostasis within methylation pathways, and to investigate how genetic and epigenetic inputs are integrated to regulate DNA methylation patterns. Addressing these aspects of epigenetic regulation will not only be important for understanding the roles of DNA methylation during normal growth and development, but they will also provide insights into the causes and consequences of dysregulation within DNA methylation pathways. Arabidopsis thaliana is an ideal system to study epigenetic processes, like DNA methylation, as it is genetically malleable, has a small genome that is highly amenable to genome-wide analyses, and is tolerant of dramatic changes in its epigenetic landscape. In addition, many of the key players and pathways involved in establishing, maintaining, and reading epigenetic modifications are conserved between plants and mammals. Given these similarities, findings regarding how specific methylation patterns are generated and modulated during development, will be applicable to analogous processes in mammals.