Maternal SMCHD1 controls both imprinted Xist expression and imprinted X chromosome inactivation

Embryonic development is dependent on the maternal supply of proteins through the oocyte, including factors setting up the adequate epigenetic patterning of the zygotic genome. We previously reported that one such factor is the epigenetic repressor SMCHD1, whose maternal supply controls autosomal imprinted expression in mouse preimplantation embryos and mid-gestation placenta. In mouse preimplantation embryos, X chromosome inactivation is also an imprinted process. Combining genomics and imaging, we show that maternal SMCHD1 is required not only for the imprinted expression of Xist in preimplantation embryos, but also for the efficient silencing of the inactive X in both the preimplantation embryo and mid-gestation placenta. These results expand the role of SMCHD1 in enforcing the silencing of Polycomb targets. The inability of zygotic SMCHD1 to fully restore imprinted X inactivation further points to maternal SMCHD1's role in setting up the appropriate chromatin environment during preimplantation development, a critical window of epigenetic remodelling. methylome and transcriptome analysis of mouse embryos with maternal deletions of Smchd1胚胎发育依赖卵母细胞提供的母源蛋白质储备，其中包含参与构建合子基因组恰当表观遗传模式的相关因子。我们此前曾报道，表观遗传阻遏因子SMCHD1便是这类因子之一：母源来源的SMCHD1可调控小鼠植入前胚胎以及妊娠中期胎盘中的常染色体印记表达。 在小鼠植入前胚胎中，X染色体失活同样属于印记调控过程。本研究结合基因组学与成像技术，证实母源SMCHD1不仅是植入前胚胎中X染色体失活特异性转录本（Xist）印记表达的必需因子，同时可在植入前胚胎与妊娠中期胎盘中高效沉默失活的X染色体。 上述结果拓展了SMCHD1在沉默多梳蛋白（Polycomb）靶基因过程中的功能。合子源性SMCHD1无法完全恢复印记X染色体失活这一现象，进一步印证了母源SMCHD1在植入前发育阶段构建恰当染色质环境的关键作用——而该阶段正是表观遗传重塑的关键窗口。 本数据集为母源Smchd1缺失小鼠胚胎的甲基化组与转录组分析数据。