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; Marnie E Blewitt

doi:10.1038/s41467-022-29333-1

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

Nat Commun. 2022 Mar 29;13(1):1658. doi: 10.1038/s41467-022-29333-1.

Authors

Andrew Keniry^{1

2}, Natasha Jansz^{3

4}, Linden J Gearing^{3

4}, Iromi Wanigasuriya^{3

4}, Joseph Chen^{5

6

7}, Christian M Nefzger^{5

8}, Peter F Hickey^{3

4}, Quentin Gouil^{3

4}, Joy Liu^{3

4}, Kelsey A Breslin³, Megan Iminitoff^{3

4}, Tamara Beck³, Andres Tapia Del Fierro^{3

4}, Lachlan Whitehead^{3

4}, Andrew Jarratt^{3

4}, Sarah A Kinkel^{3

4}, Phillippa C Taberlay⁹, Tracy Willson^{3

4}, Miha Pakusch³, Matthew E Ritchie^{3

4}, Douglas J Hilton^{3

4}, Jose M Polo^{5

6

7}, Marnie E Blewitt^{10

11}

Affiliations

¹ The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. keniry@wehi.edu.au.
² The Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia. keniry@wehi.edu.au.
³ The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
⁴ The Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
⁵ Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
⁶ Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, VIC, Australia.
⁷ Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
⁸ The University of Queensland, Institute for Molecular Bioscience, St Lucia, QLD, Australia.
⁹ School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia.
¹⁰ The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. blewitt@wehi.edu.au.
¹¹ The Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia. blewitt@wehi.edu.au.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chromatin / genetics
Dosage Compensation, Genetic
Epigenesis, Genetic
Female
Mice
RNA, Long Noncoding* / genetics
X Chromosome / genetics
X Chromosome Inactivation* / genetics

Substances

Chromatin
RNA, Long Noncoding