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Complete loss of H3K9 methylation dissolves mouse heterochromatin organization

Author

Listed:
  • Thomas Montavon

    (Max-Planck Institute of Immunobiology and Epigenetics)

  • Nicholas Shukeir

    (Max-Planck Institute of Immunobiology and Epigenetics)

  • Galina Erikson

    (Max-Planck Institute of Immunobiology and Epigenetics)

  • Bettina Engist

    (Max-Planck Institute of Immunobiology and Epigenetics)

  • Megumi Onishi-Seebacher

    (Max-Planck Institute of Immunobiology and Epigenetics
    Novartis Institute for Biomedical Research (NIBR))

  • Devon Ryan

    (Max-Planck Institute of Immunobiology and Epigenetics
    Genedata AG)

  • Yaarub Musa

    (Max-Planck Institute of Immunobiology and Epigenetics
    Thermo Fisher Scientific GmbH)

  • Gerhard Mittler

    (Max-Planck Institute of Immunobiology and Epigenetics)

  • Alexandra Graff Meyer

    (Friedrich Miescher Institute for Biomedical Research)

  • Christel Genoud

    (Friedrich Miescher Institute for Biomedical Research)

  • Thomas Jenuwein

    (Max-Planck Institute of Immunobiology and Epigenetics)

Abstract

Histone H3 lysine 9 (H3K9) methylation is a central epigenetic modification that defines heterochromatin from unicellular to multicellular organisms. In mammalian cells, H3K9 methylation can be catalyzed by at least six distinct SET domain enzymes: Suv39h1/Suv39h2, Eset1/Eset2 and G9a/Glp. We used mouse embryonic fibroblasts (MEFs) with a conditional mutation for Eset1 and introduced progressive deletions for the other SET domain genes by CRISPR/Cas9 technology. Compound mutant MEFs for all six SET domain lysine methyltransferase (KMT) genes lack all H3K9 methylation states, derepress nearly all families of repeat elements and display genomic instabilities. Strikingly, the 6KO H3K9 KMT MEF cells no longer maintain heterochromatin organization and have lost electron-dense heterochromatin. This is a compelling analysis of H3K9 methylation-deficient mammalian chromatin and reveals a definitive function for H3K9 methylation in protecting heterochromatin organization and genome integrity.

Suggested Citation

  • Thomas Montavon & Nicholas Shukeir & Galina Erikson & Bettina Engist & Megumi Onishi-Seebacher & Devon Ryan & Yaarub Musa & Gerhard Mittler & Alexandra Graff Meyer & Christel Genoud & Thomas Jenuwein, 2021. "Complete loss of H3K9 methylation dissolves mouse heterochromatin organization," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24532-8
    DOI: 10.1038/s41467-021-24532-8
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    Cited by:

    1. Maja Olecka & Alena Bömmel & Lena Best & Madlen Haase & Silke Foerste & Konstantin Riege & Thomas Dost & Stefano Flor & Otto W. Witte & Sören Franzenburg & Marco Groth & Björn Eyss & Christoph Kaleta , 2024. "Nonlinear DNA methylation trajectories in aging male mice," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Raphaël Pantier & Megan Brown & Sicheng Han & Katie Paton & Stephen Meek & Thomas Montavon & Nicholas Shukeir & Toni McHugh & David A. Kelly & Tino Hochepied & Claude Libert & Thomas Jenuwein & Tom Bu, 2024. "MeCP2 binds to methylated DNA independently of phase separation and heterochromatin organisation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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