期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-29333-1
关键词
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资金
- Australian Research Training Program scholarship
- Melbourne Research Scholarship - International
- Bellberry-Viertel Senior Medical Research Fellowship
- Sylvia and Charles Viertel Senior Medical Research Fellowship
- Australian National Health and Medical Research Council fellowship
- Australian National Health and Medical Research Council [1059624, 1194345, 1140976]
- Dyson Bequest
- DHB Foundation
- Victorian State Government Operational Infrastructure Support
- Australian National Health and Medical Research Council IRIISS grant [9000433]
- National Health and Medical Research Council of Australia [9000433, 1140976, 1059624, 1194345] Funding Source: NHMRC
In this study, a replenishable female mouse embryonic stem cell system was developed to study X chromosome inactivation (XCI). Through a targeted genetic screen, the researchers identified the BAF complex as essential for creating nucleosome-depleted regions at promoters on the inactive X chromosome during the early stages of XCI establishment. This model system provides a valuable tool for discovering unknown factors involved in XCI and epigenetic silencing.
The 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. Female embryonic stem cells (ESCs) are the ideal model to study X chromosome inactivation (XCI) establishment; however, these cells are challenging to keep in culture. Here the authors create fluorescent 'Xmas' reporter mice as a renewable source of ESCs and show nucleosome remodelers Smarcc1 and Smarca4 create a nucleosome-free promoter region prior to the establishment of silencing.
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