Conversion of random X-inactivation to imprinted X-inactivation by maternal PRC2.

Abstract

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 (<i>Eed</i>^m-/-) but not zygotic-null (<i>Eed</i>^-/-) early embryos, the maternal X-chromosome ectopically induced <i>Xist</i> and underwent inactivation. <i>Eed</i>^m-/- females subsequently stochastically silenced <i>Xist</i> from one of the two X-chromosomes and displayed random X-inactivation. This effect was exacerbated in embryos lacking both maternal and zygotic EED (<i>Eed</i>^mz-/-), suggesting that zygotic EED can also contribute to the onset of imprinted X-inactivation. <i>Xist</i> expression dynamics in <i>Eed</i>^m-/- 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.