Establishment and Modulation of DNA Methylation Patterns in Arabidopsis

拟南芥 DNA 甲基化模式的建立和调控

• 批准号: 10452655
• 负责人: Julie Ann Law
• 金额: $ 41.04万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10452655
• 关键词: Aberrant DNA Methylation; Address; Affect; Animals; Arabidopsis; Biochemical; Biological Models; Biological Process; Boundary Elements; Cell physiology; Cells; Chemicals; Chromatin; Chromatin Remodeling Factor; Complex; Cytosine; DNA; DNA Methylation; DNA-Directed RNA Polymerase; Data; Defect; Deposition; Development; Developmental Process; Disease; Elements; Ensure; Environment; Epigenetic Process; Equilibrium; Family; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Gene Silencing; Generations; Genetic; Genetic Materials; Genetic Transcription; Genome; Growth and Development function; Health; Histones; Homeostasis; Human; Immunoprecipitation; Individual; Lead; Link; Malignant Neoplasms; Mammals; Maps; Mass Spectrum Analysis; Methylation; Modeling; Modification; Mouse-ear Cress; Organism; Pathway interactions; Pattern; Plant Model; Plants; Play; Polymerase; Positioning Attribute; Process; Production; Progressive Disease; Property; Protein Family; Proteins; Reading; Regulation; Role; Site; Small Interfering RNA; Source; Specificity; Speed; System; Techniques; Testing; Tissues; Work; base; biochemical tools; cell type; chromatin modification; complex IV; epigenetic regulation; epigenome; epigenomics; experimental study; genome wide methylation; genome-wide; genome-wide analysis; genomic tools; imprint; insight; methylation pattern; mutant; novel; predictive modeling; preference; prevent; recruit; response

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.

抽象的 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。 这种显着多样性的来源之一是化学标签（例如DNA甲基化）的存在，它是装饰的 基因组和在各种生物学过程中扮演角色，包括基因调节，转座子沉默和 烙印。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有所不同，但如何 产生了这种模式，以及它们如何影响基因表达模式的理解仍然很少。作为 异常的DNA甲基化模式与植物中的发育缺陷有关，许多 人类的疾病，了解表观遗传调节的这些方面至关重要。 该实验室使用植物模型拟南芥，最近发现了一个四种相关染色质的家族 重塑因子以特异性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期间获得的见解，该提议试图了解 促进基因座特异性靶向DNA甲基化的机制，以确定检查和平衡 这使基因组规模稳态在甲基化途径中，并研究遗传和 表观遗传输入被整合以调节DNA甲基化模式。解决表观遗传的这些方面 调节不仅对于理解正常生长中DNA甲基化的作用至关重要 开发，但它们还将提供有关DNA内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（如DNA甲基化）的理想系统，因为它是遗传学上的 可延展，具有小的基因组，可与全基因组分析高度敏感，并且具有戏剧性 其表观遗传景观的变化。此外，许多关键参与者和途径涉及建立， 维持和阅读表观遗传修饰是在植物和哺乳动物之间保存的。鉴于这些 相似之处，关于如何生成和调制特定甲基化模式的发现 开发将适用于哺乳动物的类似过程。