Epigenetic Regulation of the Embryonic Germ Line

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DESCRIPTION (provided by applicant): Pluripotent stem cells have the natural capacity to generate multiple types of tissues in an organism. Germ cells give rise to all structural and reproductive lineages at each generation, and may therefore be considered the ultimate form of pluripotent stem cell. Understanding the mechanisms that maintain embryonic germ cell pluripotency will likely provide understanding of similar mechanisms used to maintain somatic stem cell lineages. Pluripotency is an essential feature of germ cells and its maintenance is tied to germ cell viability. Genome-wide transcriptional repression has been observed to play a predominant role in germ line maintenance in a number of species, including the soil nematode C. elegans. C. elegans is an animal genetic model system that has provided key insights into the regulation and mechanisms of a number of conserved processes that, when disturbed in humans, cause disease. We use this model organism to study germ cell development, and have identified a highly conserved mode of germ line maintenance that involves establishment and maintenance of specific chromatin architecture. This process is essential for germ cell survival and maintenance, and therefore is essential for maintaining a pluripotent cell type. Understanding how the unique germ cell chromatin architecture is established and maintained will be key to our understanding of germ cell maintenance. This will provide insights into how transcriptional programs can be regulated or repressed at the level of the genome, which could prove useful for targeting tumor cells for growth repression. This could also provide a better foundation for understanding how pluripotency is achieved and hopefully lead to therapies involving somatic stem cells.