PT - JOURNAL ARTICLE AU - Iromi Wanigasuriya AU - Sarah A Kinkel AU - Tamara Beck AU - Ellise A Roper AU - Kelsey Breslin AU - Heather J Lee AU - Andrew Keniry AU - Matthew E Ritchie AU - Marnie E Blewitt AU - Quentin Gouil TI - Maternal SMCHD1 controls both imprinted <em>Xist</em> expression and imprinted X chromosome inactivation AID - 10.1101/2021.10.21.465360 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.10.21.465360 4099 - http://biorxiv.org/content/early/2021/10/21/2021.10.21.465360.short 4100 - http://biorxiv.org/content/early/2021/10/21/2021.10.21.465360.full AB - 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.Competing Interest StatementThe authors have declared no competing interest.