Keniry, A.Jansz, N.Gearing, L.J.Wanigasuriya, I.Chen, J.Nefzger, C.M.Hickey, P.F.Gouil, Q.Liu, J.Breslin, K.A.Iminitoff, M.Beck, T.Tapia Del Fierro, A.Whitehead, L.Jarratt, A.Kinkel, S.A.Taberlay, P.C.Willson, T.Pakusch, M.Ritchie, M.E.et al.2022-10-312022-10-312022Nature Communications, 2022; 13(1):1-152041-17232041-1723https://hdl.handle.net/2440/136795The process of epigenetic silencing, while fundamentally important, is not yet completely understood. Here we report a replenishable female mouse embryonic stem cell (mESC) system, Xmas, that allows rapid assessment of X chromosome inactivation (XCI), the epigenetic silencing mechanism of one of the two X chromosomes that enables dosage compensation in female mammals. Through a targeted genetic screen in differentiating Xmas mESCs, we reveal that the BAF complex is required to create nucleosome-depleted regions at promoters on the inactive X chromosome during the earliest stages of establishment of XCI. Without this action gene silencing fails. Xmas mESCs provide a tractable model for screen-based approaches that enable the discovery of unknown facets of the female-specific process of XCI and epigenetic silencing more broadly.en© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.X ChromosomeChromatinAnimalsMiceEpigenesis, GeneticDosage Compensation, GeneticFemaleX Chromosome InactivationRNA, Long NoncodingX ChromosomeChromatinAnimalsMiceEpigenesis, GeneticDosage Compensation, GeneticFemaleX Chromosome InactivationRNA, Long NoncodingJournal article10.1038/s41467-022-29333-12022-10-31608319Polo, J.M. [0000-0002-2531-778X]