Abstract
Early embryogenesis is accompanied by dynamic epigenetic modifications. While such dynamics are important in cell intrinsic regulation of gene expression, their extrinsic roles in mediating intercellular communication during early embryogenesis is less understood. Using the dTAG system, here we reveal previously underappreciated stage-specific functions of PRC2 in regulating pre-implantation and primordial germ cell (PGC) development. We demonstrate that PRC2 plays important roles in regulating maternal to zygotic transition (MZT), and epiblast (EPI) formation. By systematically analyzing H3K27me3 and H3K4me3 dynamics, we redefine the timing of bivalency establishment and uncover a stepwise mechanism governing bivalency acquisition in early embryogenesis. Moreover, PRC2 regulates proper PGC numbers in the EPI by controlling Esrrb expression in the extraembryonic ectoderm (ExE). Thus, our study uncovers a previously unknown cell-autonomous function of PRC2 in preimplantation development and its non-cell-autonomous impact in PGC number regulation, both through interplays between epigenetic-epigenetic and epigenetic-TFs networks.
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Abstract
Early embryogenesis is accompanied by dynamic epigenetic modifications. While such dynamics are important in cell intrinsic regulation of gene expression, their extrinsic roles in mediating intercellular communication during early embryogenesis is less understood. Using the protein degradation tag (dTAG) system, here we decode stage- and lineage-specific functions of Eed, a core component of Polycomb Repressive Complex 2 (PRC2) in mouse early embryogenesis. Our results reveal previously underappreciated cell intrinsic and extrinsic functions of PRC2 in regulating pre-implantation and primordial germ cell (PGC) development, respectively. We demonstrate that PRC2 is required for normal maternal to zygotic transition (MZT), and epiblast (EPI) specification. Moreover, PRC2 controls proper PGC numbers in EPI through a PRC2-ESRRB-BMP4 regulatory axis in extraembryonic ectoderm (ExE). Thus, our study uncovers a previously unknown cell-autonomous function of PRC2 in preimplantation development and its non-cell-autonomous function in PGC number regulation, both through interplays between epigenetic-epigenetic and epigenetic-TFs networks.
Competing Interest Statement
The authors have declared no competing interest.
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