Thursday, November 21, 2024
11/21/2024
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.
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