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Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing

Author

Listed:
  • Kentaro Mochizuki

    (University of British Columbia)

  • Jafar Sharif

    (RIKEN Center for Integrative Medical Sciences (IMS))

  • Kenjiro Shirane

    (University of British Columbia
    Kyushu University)

  • Kousuke Uranishi

    (Saitama Medical University)

  • Aaron B. Bogutz

    (University of British Columbia)

  • Sanne M. Janssen

    (University of British Columbia)

  • Ayumu Suzuki

    (Saitama Medical University)

  • Akihiko Okuda

    (Saitama Medical University)

  • Haruhiko Koseki

    (RIKEN Center for Integrative Medical Sciences (IMS)
    Chiba University)

  • Matthew C. Lorincz

    (University of British Columbia)

Abstract

Silencing of a subset of germline genes is dependent upon DNA methylation (DNAme) post-implantation. However, these genes are generally hypomethylated in the blastocyst, implicating alternative repressive pathways before implantation. Indeed, in embryonic stem cells (ESCs), an overlapping set of genes, including germline “genome-defence” (GGD) genes, are upregulated following deletion of the H3K9 methyltransferase SETDB1 or subunits of the non-canonical PRC1 complex PRC1.6. Here, we show that in pre-implantation embryos and naïve ESCs (nESCs), hypomethylated promoters of germline genes bound by the PRC1.6 DNA-binding subunits MGA/MAX/E2F6 are enriched for RING1B-dependent H2AK119ub1 and H3K9me3. Accordingly, repression of these genes in nESCs shows a greater dependence on PRC1.6 than DNAme. In contrast, GGD genes are hypermethylated in epiblast-like cells (EpiLCs) and their silencing is dependent upon SETDB1, PRC1.6/RING1B and DNAme, with H3K9me3 and DNAme establishment dependent upon MGA binding. Thus, GGD genes are initially repressed by PRC1.6, with DNAme subsequently engaged in post-implantation embryos.

Suggested Citation

  • Kentaro Mochizuki & Jafar Sharif & Kenjiro Shirane & Kousuke Uranishi & Aaron B. Bogutz & Sanne M. Janssen & Ayumu Suzuki & Akihiko Okuda & Haruhiko Koseki & Matthew C. Lorincz, 2021. "Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27345-x
    DOI: 10.1038/s41467-021-27345-x
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    as
    1. Simon J. Elsässer & Kyung-Min Noh & Nichole Diaz & C. David Allis & Laura A. Banaszynski, 2015. "Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells," Nature, Nature, vol. 522(7555), pages 240-244, June.
    2. Ayumu Suzuki & Masataka Hirasaki & Tomoaki Hishida & Jun Wu & Daiji Okamura & Atsushi Ueda & Masazumi Nishimoto & Yutaka Nakachi & Yosuke Mizuno & Yasushi Okazaki & Yasuhisa Matsui & Juan Carlos Izpis, 2016. "Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells," Nature Communications, Nature, vol. 7(1), pages 1-15, April.
    3. Helen M. Rowe & Johan Jakobsson & Daniel Mesnard & Jacques Rougemont & Séverine Reynard & Tugce Aktas & Pierre V. Maillard & Hillary Layard-Liesching & Sonia Verp & Julien Marquis & François Spitz & D, 2010. "KAP1 controls endogenous retroviruses in embryonic stem cells," Nature, Nature, vol. 463(7278), pages 237-240, January.
    4. Thomas Dahlet & Matthias Truss & Ute Frede & Hala Al Adhami & Anaïs F. Bardet & Michael Dumas & Judith Vallet & Johana Chicher & Philippe Hammann & Sarah Kottnik & Peter Hansen & Uschi Luz & Gonzalo A, 2021. "E2F6 initiates stable epigenetic silencing of germline genes during embryonic development," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    5. Dominik Hoelper & Hongda Huang & Aayushi Y. Jain & Dinshaw J. Patel & Peter W. Lewis, 2017. "Structural and mechanistic insights into ATRX-dependent and -independent functions of the histone chaperone DAXX," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    6. Roshan M. Kumar & Patrick Cahan & Alex K. Shalek & Rahul Satija & A. Jay DaleyKeyser & Hu Li & Jin Zhang & Keith Pardee & David Gennert & John J. Trombetta & Thomas C. Ferrante & Aviv Regev & George Q, 2014. "Deconstructing transcriptional heterogeneity in pluripotent stem cells," Nature, Nature, vol. 516(7529), pages 56-61, December.
    7. Daniel N. Weinberg & Simon Papillon-Cavanagh & Haifen Chen & Yuan Yue & Xiao Chen & Kartik N. Rajagopalan & Cynthia Horth & John T. McGuire & Xinjing Xu & Hamid Nikbakht & Agata E. Lemiesz & Dylan M. , 2019. "The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape," Nature, Nature, vol. 573(7773), pages 281-286, September.
    8. Shihori Yokobayashi & Ching-Yeu Liang & Hubertus Kohler & Peter Nestorov & Zichuan Liu & Miguel Vidal & Maarten van Lohuizen & Tim C. Roloff & Antoine H. F. M. Peters, 2013. "PRC1 coordinates timing of sexual differentiation of female primordial germ cells," Nature, Nature, vol. 495(7440), pages 236-240, March.
    9. Elisa Lavarone & Caterina M. Barbieri & Diego Pasini, 2019. "Dissecting the role of H3K27 acetylation and methylation in PRC2 mediated control of cellular identity," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    10. Veronika Ostapcuk & Fabio Mohn & Sarah H. Carl & Anja Basters & Daniel Hess & Vytautas Iesmantavicius & Lisa Lampersberger & Matyas Flemr & Aparna Pandey & Nicolas H. Thomä & Joerg Betschinger & Marc , 2018. "Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes," Nature, Nature, vol. 557(7707), pages 739-743, May.
    11. Thomas Dahlet & Andrea Argüeso Lleida & Hala Al Adhami & Michael Dumas & Ambre Bender & Richard P. Ngondo & Manon Tanguy & Judith Vallet & Ghislain Auclair & Anaïs F. Bardet & Michael Weber, 2020. "Genome-wide analysis in the mouse embryo reveals the importance of DNA methylation for transcription integrity," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    12. Stefanie Grosswendt & Helene Kretzmer & Zachary D. Smith & Abhishek Sampath Kumar & Sara Hetzel & Lars Wittler & Sven Klages & Bernd Timmermann & Shankar Mukherji & Alexander Meissner, 2020. "Epigenetic regulator function through mouse gastrulation," Nature, Nature, vol. 584(7819), pages 102-108, August.
    13. Toshiyuki Matsui & Danny Leung & Hiroki Miyashita & Irina A. Maksakova & Hitoshi Miyachi & Hiroshi Kimura & Makoto Tachibana & Matthew C. Lorincz & Yoichi Shinkai, 2010. "Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET," Nature, Nature, vol. 464(7290), pages 927-931, April.
    14. Jiho Choi & Aaron J. Huebner & Kendell Clement & Ryan M. Walsh & Andrej Savol & Kaixuan Lin & Hongcang Gu & Bruno Di Stefano & Justin Brumbaugh & Sang-Yong Kim & Jafar Sharif & Christopher M. Rose & A, 2017. "Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells," Nature, Nature, vol. 548(7666), pages 219-223, August.
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