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

Author

Listed:
  • Andrew Keniry

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Natasha Jansz

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Linden J. Gearing

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Iromi Wanigasuriya

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Joseph Chen

    (Monash University
    Monash Biomedicine Discovery Institute
    Monash University)

  • Christian M. Nefzger

    (Monash University
    Institute for Molecular Bioscience)

  • Peter F. Hickey

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Quentin Gouil

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Joy Liu

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Kelsey A. Breslin

    (The Walter and Eliza Hall Institute of Medical Research)

  • Megan Iminitoff

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Tamara Beck

    (The Walter and Eliza Hall Institute of Medical Research)

  • Andres Tapia del Fierro

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Lachlan Whitehead

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Andrew Jarratt

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Sarah A. Kinkel

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Phillippa C. Taberlay

    (University of Tasmania)

  • Tracy Willson

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Miha Pakusch

    (The Walter and Eliza Hall Institute of Medical Research)

  • Matthew E. Ritchie

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Douglas J. Hilton

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Jose M. Polo

    (Monash University
    Monash Biomedicine Discovery Institute
    Monash University)

  • Marnie E. Blewitt

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

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.

Suggested Citation

  • 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 B, 2022. "BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29333-1
    DOI: 10.1038/s41467-022-29333-1
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    References listed on IDEAS

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    Cited by:

    1. Natalia Benetti & Quentin Gouil & Andres Tapia del Fierro & Tamara Beck & Kelsey Breslin & Andrew Keniry & Edwina McGlinn & Marnie E. Blewitt, 2022. "Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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