Establishment and Modulation of DNA Methylation Patterns in Arabidopsis

摘要 在任何给定的生物体中，每个细胞都具有基本相同的遗传物质，但并非所有细胞的行为都相似。 这种显著多样性的一个来源是化学标签的存在，如DNA甲基化， 基因组和发挥作用的各种生物过程，包括基因调控，转座子沉默， 印记虽然已知DNA甲基化的模式在组织或细胞类型之间可能不同，但如何 这些模式的产生以及它们如何影响基因表达模式仍然知之甚少。作为 异常的DNA甲基化模式与植物中的发育缺陷以及许多 在人类疾病中，了解表观遗传调控的这些方面至关重要。 利用植物模型拟南芥，该实验室最近发现了一个四个相关染色质家族 重塑因子以基因座和组织特异性方式控制DNA甲基化模式。基于新 在这些染色质调节剂的表征过程中获得的见解，该提案旨在了解 促进基因座特异性靶向DNA甲基化的机制，以确定制衡 使基因组规模的甲基化途径内的稳态，并研究如何遗传和 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 调控不仅对理解DNA甲基化在正常生长过程中的作用很重要， 发展，但他们也将提供深入了解的原因和后果失调的DNA 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，因为它在遗传上是 可塑性，具有小的基因组，非常适合全基因组分析，并且能够容忍戏剧性的 表观遗传景观的变化此外，许多参与建立的关键角色和途径， 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。鉴于这些 相似之处，关于特定甲基化模式如何产生和调节的发现， 开发，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.