Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
The Department of Medical Biology, The University of Melbourne, Parkville, Australia.
Epigenetics Chromatin. 2022 Jul 18;15(1):26. doi: 10.1186/s13072-022-00458-3.
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.
胚胎发育依赖于卵母细胞中母体提供的蛋白质，包括为合子基因组建立适当表观遗传模式的因素。我们之前报道过，这样的一个因素是表观遗传抑制剂 SMCHD1，其母体供应控制着小鼠着床前胚胎和中期胎盘的常染色体印迹表达。在小鼠着床前胚胎中，X 染色体失活也是一个印迹过程。通过基因组学和成像技术的结合，我们表明，母体 SMCHD1 不仅需要印迹表达 Xist 在着床前胚胎中，而且需要在着床前胚胎和中期胎盘高效沉默失活的 X 染色体。这些结果扩展了 SMCHD1 在强制沉默 Polycomb 靶标的作用。合子 SMCHD1 不能完全恢复印迹 X 染色体失活进一步表明，母体 SMCHD1 在着床前发育过程中（即表观遗传重塑的关键窗口）建立适当染色质环境方面发挥作用。
