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SMARCAD1 ATPase activity is required to silence endogenous retroviruses in embryonic stem cells

Author

Listed:
  • Parysatis Sachs

    (Philipps University Marburg)

  • Dong Ding

    (Philipps University Marburg)

  • Philipp Bergmaier

    (Philipps University Marburg)

  • Boris Lamp

    (Philipps University Marburg)

  • Christina Schlagheck

    (Philipps University Marburg)

  • Florian Finkernagel

    (Philipps University Marburg)

  • Andrea Nist

    (Philipps University Marburg)

  • Thorsten Stiewe

    (Philipps University Marburg)

  • Jacqueline E. Mermoud

    (Philipps University Marburg)

Abstract

Endogenous retroviruses (ERVs) can confer benefits to their host but present a threat to genome integrity if not regulated correctly. Here we identify the SWI/SNF-like remodeler SMARCAD1 as a key factor in the control of ERVs in embryonic stem cells. SMARCAD1 is enriched at ERV subfamilies class I and II, particularly at active intracisternal A-type particles (IAPs), where it preserves repressive histone methylation marks. Depletion of SMARCAD1 results in de-repression of IAPs and adjacent genes. Recruitment of SMARCAD1 to ERVs is dependent on KAP1, a central component of the silencing machinery. SMARCAD1 and KAP1 occupancy at ERVs is co-dependent and requires the ATPase function of SMARCAD1. Our findings uncover a role for the enzymatic activity of SMARCAD1 in cooperating with KAP1 to silence ERVs. This reveals ATP-dependent chromatin remodeling as an integral step in retrotransposon regulation in stem cells and advances our understanding of the mechanisms driving heterochromatin establishment.

Suggested Citation

  • Parysatis Sachs & Dong Ding & Philipp Bergmaier & Boris Lamp & Christina Schlagheck & Florian Finkernagel & Andrea Nist & Thorsten Stiewe & Jacqueline E. Mermoud, 2019. "SMARCAD1 ATPase activity is required to silence endogenous retroviruses in embryonic stem cells," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09078-0
    DOI: 10.1038/s41467-019-09078-0
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    Cited by:

    1. Sophia Groh & Anna Viktoria Milton & Lisa Katherina Marinelli & Cara V. Sickinger & Angela Russo & Heike Bollig & Gustavo Pereira de Almeida & Andreas Schmidt & Ignasi Forné & Axel Imhof & Gunnar Scho, 2021. "Morc3 silences endogenous retroviruses by enabling Daxx-mediated histone H3.3 incorporation," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Marko Dunjić & Felix Jonas & Gilad Yaakov & Roye More & Yoav Mayshar & Yoach Rais & Ayelet-Hashahar Orenbuch & Saifeng Cheng & Naama Barkai & Yonatan Stelzer, 2023. "Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Sandhya Chandrasekaran & Sergio Espeso-Gil & Yong-Hwee Eddie Loh & Behnam Javidfar & Bibi Kassim & Yueyan Zhu & Yuan Zhang & Yuhao Dong & Lucy K. Bicks & Haixin Li & Prashanth Rajarajan & Cyril J. Pet, 2021. "Neuron-specific chromosomal megadomain organization is adaptive to recent retrotransposon expansions," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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