BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation

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 ()
Additional contact information
Andrew Keniry: The Walter and Eliza Hall Institute of Medical Research
Natasha Jansz: The Walter and Eliza Hall Institute of Medical Research
Linden J. Gearing: The Walter and Eliza Hall Institute of Medical Research
Iromi Wanigasuriya: The Walter and Eliza Hall Institute of Medical Research
Joseph Chen: Monash University
Christian M. Nefzger: Monash University
Peter F. Hickey: The Walter and Eliza Hall Institute of Medical Research
Quentin Gouil: The Walter and Eliza Hall Institute of Medical Research
Joy Liu: The Walter and Eliza Hall Institute of Medical Research
Kelsey A. Breslin: The Walter and Eliza Hall Institute of Medical Research
Megan Iminitoff: The Walter and Eliza Hall Institute of Medical Research
Tamara Beck: The Walter and Eliza Hall Institute of Medical Research
Andres Tapia del Fierro: The Walter and Eliza Hall Institute of Medical Research
Lachlan Whitehead: The Walter and Eliza Hall Institute of Medical Research
Andrew Jarratt: The Walter and Eliza Hall Institute of Medical Research
Sarah A. Kinkel: The Walter and Eliza Hall Institute of Medical Research
Phillippa C. Taberlay: University of Tasmania
Tracy Willson: The Walter and Eliza Hall Institute of Medical Research
Miha Pakusch: The Walter and Eliza Hall Institute of Medical Research
Matthew E. Ritchie: The Walter and Eliza Hall Institute of Medical Research
Douglas J. Hilton: The Walter and Eliza Hall Institute of Medical Research
Jose M. Polo: Monash University
Marnie E. Blewitt: The Walter and Eliza Hall Institute of Medical Research

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29333-1

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