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A somatic role for the histone methyltransferase Setdb1 in endogenous retrovirus silencing

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  • Masaki Kato

    (RIKEN)

  • Keiko Takemoto

    (Kyoto University)

  • Yoichi Shinkai

    (RIKEN)

Abstract

Subsets of endogenous retroviruses (ERVs) are derepressed in mouse embryonic stem cells (mESCs) deficient for Setdb1, which catalyzes histone H3 lysine 9 trimethylation (H3K9me3). Most of those ERVs, including IAPs, remain silent if Setdb1 is deleted in differentiated embryonic cells; however they are derepressed when deficient for Dnmt1, suggesting that Setdb1 is dispensable for ERV silencing in somatic cells. However, H3K9me3 enrichment on ERVs is maintained in differentiated cells and is mostly diminished in mouse embryonic fibroblasts (MEFs) lacking Setdb1. Here we find that distinctive sets of ERVs are reactivated in different types of Setdb1-deficient somatic cells, including the VL30-class of ERVs in MEFs, whose derepression is dependent on cell-type-specific transcription factors (TFs). These data suggest a more general role for Setdb1 in ERV silencing, which provides an additional layer of epigenetic silencing through the H3K9me3 modification.

Suggested Citation

  • Masaki Kato & Keiko Takemoto & Yoichi Shinkai, 2018. "A somatic role for the histone methyltransferase Setdb1 in endogenous retrovirus silencing," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04132-9
    DOI: 10.1038/s41467-018-04132-9
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    Cited by:

    1. Phoebe Lut Fei Tam & Ming Fung Cheung & Lu Yan Chan & Danny Leung, 2024. "Cell-type differential targeting of SETDB1 prevents aberrant CTCF binding, chromatin looping, and cis-regulatory interactions," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. 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.
    3. Poonam Dhillon & Kelly Ann Mulholland & Hailong Hu & Jihwan Park & Xin Sheng & Amin Abedini & Hongbo Liu & Allison Vassalotti & Junnan Wu & Katalin Susztak, 2023. "Increased levels of endogenous retroviruses trigger fibroinflammation and play a role in kidney disease development," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Zeyang Wang & Rui Fan & Angela Russo & Filippo M. Cernilogar & Alexander Nuber & Silvia Schirge & Irina Shcherbakova & Iva Dzhilyanova & Enes Ugur & Tobias Anton & Lisa Richter & Heinrich Leonhardt & , 2022. "Dominant role of DNA methylation over H3K9me3 for IAP silencing in endoderm," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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