GSE123173
Switching from Random to Imprinted X-inactivation by Maternal PRC2
Imprinted X-inactivation is a paradigm of transgenerational epigenetic inheritance in mammals and silences genes exclusively on the paternally-inherited X-chromosome.  Here, we test the hypothesis that oocyte-derived maternal Polycomb repressive complex 2 (PRC2) protein EED orchestrates the selective inactivation of the paternal-X in mouse embryos.  In maternal Eed null (Eedm-/-) but not zygotic Eed null female and male embryos, the maternal X-chromosome ectopically induced Xist lncRNA, which silences X-linked genes.  Subsequently, Xist was silenced from one of the two X-chromosomes in females and from the sole maternal-X in males.  As a result, later-stage female Eedm-/- embryos displayed random X-inactivation.  The kinetics of Xist RNA induction in Eedm-/- embryos resemble that of early human embryos, which lack oocyte-derived PRC2 and only undergo random X-inactivation.  Thus, expression of PRC2 genes in the oocyte and transmission of the gene products to the embryo may dictate the occurrence of imprinted X-inactivation in mammals. Overall design: Allele-specific mRNA profile of Eedfl/fl, Eedfl/-, Eed-/-, Eedm-/-, and Eedmz-/- mouse E3.5 embryos by RNA-Seq