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Publication : Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte.

First Author  Hill PWS Year  2018
Journal  Nature Volume  555
Issue  7696 Pages  392-396
PubMed ID  29513657 Mgi Jnum  J:261805
Mgi Id  MGI:6154788 Doi  10.1038/nature25964
Citation  Hill PWS, et al. (2018) Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte. Nature 555(7696):392-396
abstractText  Gametes are highly specialized cells that can give rise to the next generation through their ability to generate a totipotent zygote. In mice, germ cells are first specified in the developing embryo around embryonic day (E) 6.25 as primordial germ cells (PGCs). Following subsequent migration into the developing gonad, PGCs undergo a wave of extensive epigenetic reprogramming around E10.5-E11.5, including genome-wide loss of 5-methylcytosine. The underlying molecular mechanisms of this process have remained unclear, leading to our inability to recapitulate this step of germline development in vitro. Here we show, using an integrative approach, that this complex reprogramming process involves coordinated interplay among promoter sequence characteristics, DNA (de)methylation, the polycomb (PRC1) complex and both DNA demethylation-dependent and -independent functions of TET1 to enable the activation of a critical set of germline reprogramming-responsive genes involved in gamete generation and meiosis. Our results also reveal an unexpected role for TET1 in maintaining but not driving DNA demethylation in gonadal PGCs. Collectively, our work uncovers a fundamental biological role for gonadal germline reprogramming and identifies the epigenetic principles of the PGC-to-gonocyte transition that will help to guide attempts to recapitulate complete gametogenesis in vitro.
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