1. Cell Biology
  2. Stem Cells and Regenerative Medicine
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PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes

  1. Mitsuhiro Endoh  Is a corresponding author
  2. Takaho A Endo
  3. Jun Shinga
  4. Katsuhiko Hayashi
  5. Anca Farcas
  6. Kit-Wan Ma
  7. Shinsuke Ito
  8. Jafar Sharif
  9. Tamie Endoh
  10. Naoko Onaga
  11. Manabu Nakayama
  12. Tomoyuki Ishikura
  13. Osamu Masui
  14. Benedikt M Kessler
  15. Toshio Suda
  16. Osamu Ohara
  17. Akihiko Okuda
  18. Robert J Klose
  19. Haruhiko Koseki  Is a corresponding author
  1. RIKEN Center for Integrative Medical Sciences, Japan
  2. Faculty of Medical Sciences, Kyushu University, Japan
  3. Oxford University, United Kingdom
  4. Kazusa DNA Research Institute, Japan
  5. University of Oxford, United Kingdom
  6. National University of Singapore, Singapore
  7. Saitama Medical University, Japan
  8. Faculty of Medical Sciences, Kyushu University, United Kingdom
Research Article
  • Cited 25
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Cite this article as: eLife 2017;6:e21064 doi: 10.7554/eLife.21064

Abstract

The ring finger protein PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability. We also find a role for PCGF6 in pre- and peri-implantation mouse embryonic development. We further show that a heterodimer of the transcription factors MAX and MGA recruits PCGF6 to target loci. PCGF6 thus links sequence specific target recognition by the MAX/MGA complex to PRC1-dependent transcriptional silencing of germ cell-specific genes in pluripotent stem cells.

Article and author information

Author details

  1. Mitsuhiro Endoh

    Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    For correspondence
    csime@nus.edu.sg
    Competing interests
    The authors declare that no competing interests exist.
  2. Takaho A Endo

    Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Jun Shinga

    Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Katsuhiko Hayashi

    Department of Developmental Stem Cell Biology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Anca Farcas

    Department of Biochemistry, Oxford University, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Kit-Wan Ma

    Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Shinsuke Ito

    Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  8. Jafar Sharif

    Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  9. Tamie Endoh

    Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  10. Naoko Onaga

    Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  11. Manabu Nakayama

    Chromosome Engineering Team, Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan
    Competing interests
    The authors declare that no competing interests exist.
  12. Tomoyuki Ishikura

    Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  13. Osamu Masui

    Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  14. Benedikt M Kessler

    TDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  15. Toshio Suda

    Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  16. Osamu Ohara

    Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  17. Akihiko Okuda

    Division of Developmental Biology, Saitama Medical University, Hidaka, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5298-5564
  18. Robert J Klose

    Department of Developmental Stem Cell Biology, Faculty of Medical Sciences, Kyushu University, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8726-7888
  19. Haruhiko Koseki

    Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    For correspondence
    haruhiko.koseki@riken.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8424-5854

Funding

RIKEN

  • Haruhiko Koseki

Ministry of Education, Culture, Sports, Science, and Technology

  • Haruhiko Koseki

Japan Science and Technology Agency (Strategic Basic Research Programs)

  • Haruhiko Koseki

Ministry of Education, Culture, Sports, Science, and Technology (Grant-in-Aid for Scientific Research on Innovative Areas (#26112516))

  • Mitsuhiro Endoh

Ministry of Education, Culture, Sports, Science, and Technology (Grant-in-Aid for Young Scientist (B) (#25871129))

  • Mitsuhiro Endoh

Ministry of Education, Culture, Sports, Science, and Technology (Grant-in-Aid for Scientific Research (C) (#16K07372))

  • Mitsuhiro Endoh

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were carried out according to the in-house guidelines for the care and use of laboratory animals of the RIKEN Center for Integrative Medical Sciences, Yokohama, Japan [Approval number: Kei-27-001(7)].

Reviewing Editor

  1. Robb Krumlauf, Stowers Institute for Medical Research, United States

Publication history

  1. Received: September 1, 2016
  2. Accepted: March 15, 2017
  3. Accepted Manuscript published: March 17, 2017 (version 1)
  4. Version of Record published: March 31, 2017 (version 2)
  5. Version of Record updated: April 25, 2017 (version 3)

Copyright

© 2017, Endoh et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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