Imprinted X-inactivation silences genes exclusively on the paternally-inherited X-chromosome and is a paradigm of transgenerational epigenetic inheritance in mammals. Here, we test the role of maternal vs. zygotic Polycomb repressive complex 2 (PRC2) protein EED in orchestrating imprinted X-inactivation in mouse embryos. In maternal-null () but not zygotic-null () early embryos, the maternal X-chromosome ectopically induced and underwent inactivation. females subsequently stochastically silenced from one of the two X-chromosomes and displayed random X-inactivation. This effect was exacerbated in embryos lacking both maternal and zygotic EED (), suggesting that zygotic EED can also contribute to the onset of imprinted X-inactivation. expression dynamics in embryos resemble that of early human embryos, which lack oocyte-derived maternal PRC2 and only undergo random X-inactivation. Thus, expression of PRC2 in the oocyte and transmission of the gene products to the embryo may dictate the occurrence of imprinted X-inactivation in mammals.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541438PMC
http://dx.doi.org/10.7554/eLife.44258DOI Listing

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