1. BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation.
- Author
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Keniry, Andrew, Jansz, Natasha, Gearing, Linden J., Wanigasuriya, Iromi, Chen, Joseph, Nefzger, Christian M., Hickey, Peter F., Gouil, Quentin, Liu, Joy, Breslin, Kelsey A., Iminitoff, Megan, Beck, Tamara, Tapia del Fierro, Andres, Whitehead, Lachlan, Jarratt, Andrew, Kinkel, Sarah A., Taberlay, Phillippa C., Willson, Tracy, Pakusch, Miha, and Ritchie, Matthew E.
- Subjects
X chromosome ,CHROMATIN ,EMBRYONIC stem cells ,PROMOTERS (Genetics) ,GENE silencing ,GENETIC testing ,CHRISTMAS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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