Genomic imprinting regulates parental origin-dependent monoallelic gene expression. It is mediated by either germline differential methylation of DNA (canonical imprinting) or oocyte-derived H3K27me3 (noncanonical imprinting) in mice. Depletion of Eed, an essential component of Polycomb repressive complex 2, results in genome-wide loss of H3K27me3 in oocytes, which causes loss of noncanonical imprinting (LOI) in embryos. Although Eed maternal KO (matKO) embryos show partial lethality after implantation, it is unknown whether LOI itself contributes to the developmental phenotypes of these embryos, which makes it unclear whether noncanonical imprinting is developmentally relevant. Here, by combinatorial matKO of Xist, a noncanonical imprinted gene whose LOI causes aberrant transient maternal X-chromosome inactivation (XCI) at preimplantation, we show that prevention of the transient maternal XCI greatly restores the development of Eed matKO embryos. Moreover, we found that the placentae of Eed matKO embryos are remarkably enlarged in a manner independent of Xist LOI. Heterozygous deletion screening of individual autosomal noncanonical imprinted genes suggests that LOI of the Sfmbt2 miRNA cluster chromosome 2 miRNA cluster (C2MC), solute carrier family 38 member 4 (Slc38a4), and Gm32885 contributes to the placental enlargement. Taken together, our study provides evidence that Xist imprinting sustains embryonic development and that autosomal noncanonical imprinting restrains placental overgrowth.

中文翻译：

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非规范印记维持胚胎发育并抑制胎盘过度生长

基因组印记调节父母起源依赖性单等位基因表达。它由小鼠中 DNA 的种系差异甲基化（典型印记）或卵母细胞衍生的 H3K27me3（非典型印记）介导。Eed 是 Polycomb 抑制复合物 2 的重要组成部分，其耗尽会导致卵母细胞中 H3K27me3 的全基因组丢失，从而导致胚胎中非规范印记 (LOI) 的丢失。尽管Eed母体 KO (matKO) 胚胎在植入后显示出部分致死性，但尚不清楚 LOI 本身是否有助于这些胚胎的发育表型，这使得非规范印记是否与发育相关尚不清楚。在这里，通过Xist的组合 matKO，一种非典型的印记基因，其 LOI 在植入前会导致异常的母体 X 染色体失活 (XCI)，我们表明预防短暂的母体 XCI 极大地恢复了Eed matKO 胚胎的发育。此外，我们发现Eed matKO 胚胎的胎盘以独立于Xist LOI的方式显着增大。对个体常染色体非典型印记基因的杂合缺失筛选表明，Sfmbt2 miRNA 簇染色体 2 miRNA 簇 (C2MC)、溶质载体家族 38 成员 4 ( Slc38a4 ) 和Gm32885的 LOI 有助于胎盘增大。总之，我们的研究提供了Xist印记维持胚胎发育，常染色体非典型印记抑制胎盘过度生长。