1. BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation
- Author
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Andrew Keniry, Natasha Jansz, Linden J. Gearing, Iromi Wanigasuriya, Joseph Chen, Christian M. Nefzger, Peter F. Hickey, Quentin Gouil, Joy Liu, Kelsey A. Breslin, Megan Iminitoff, Tamara Beck, Andres Tapia del Fierro, Lachlan Whitehead, Andrew Jarratt, Sarah A. Kinkel, Phillippa C. Taberlay, Tracy Willson, Miha Pakusch, Matthew E. Ritchie, Douglas J. Hilton, Jose M. Polo, and Marnie E. Blewitt
- Subjects
Mice ,X Chromosome ,Multidisciplinary ,X Chromosome Inactivation ,Dosage Compensation, Genetic ,Animals ,General Physics and Astronomy ,Female ,RNA, Long Noncoding ,General Chemistry ,Chromatin ,General Biochemistry, Genetics and Molecular Biology ,Epigenesis, Genetic - 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.
- Published
- 2022
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