STELLA modulates transcriptional and endogenous retrovirus programs during maternal-to-zygotic transition

  1. Yun Huang
  2. Jong Kyoung Kim
  3. Dang Vinh Do
  4. Caroline Lee
  5. Christopher A Penfold
  6. Jan J Zylicz
  7. John C Marioni  Is a corresponding author
  8. Jamie A Hackett  Is a corresponding author
  9. M Azim Surani  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea
  3. European Molecular Biology Laboratory - European Bioinformatics Institute, United Kingdom
  4. European Molecular Biology Laboratory, Italy

Abstract

The maternal-to-zygotic transition (MZT) marks the period when the embryonic genome is activated and acquires control of development. Maternally inherited factors play a key role in this critical developmental process, which occurs at the 2-cell stage in mice. We investigated the function of the maternally inherited factor STELLA (DPPA3) using single-cell/embryo approaches. We show that loss of maternal STELLA results in widespread transcriptional mis-regulation and a partial failure of MZT. Strikingly, activation of endogenous retroviruses (ERVs) is significantly impaired in Stella maternal/zygotic knockout embryos, which in turn leads to a failure to upregulate chimeric transcripts. Amongst ERVs, MuERV-L activation is particularly affected by the absence of STELLA, and direct in vivo knockdown of MuERV-L impacts the developmental potential of the embryo. We propose that STELLA is involved in ensuring activation of ERVs, which themselves play a potentially key role during early development, either directly or through influencing embryonic gene expression.

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The following previously published data sets were used

Article and author information

Author details

  1. Yun Huang

    Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Jong Kyoung Kim

    Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  3. Dang Vinh Do

    Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Caroline Lee

    Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Christopher A Penfold

    Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Jan J Zylicz

    Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9622-5658
  7. John C Marioni

    European Molecular Biology Laboratory - European Bioinformatics Institute, Cambridge, United Kingdom
    For correspondence
    marioni@ebi.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  8. Jamie A Hackett

    European Molecular Biology Laboratory, Rome, Italy
    For correspondence
    jamie.hackett@embl.it
    Competing interests
    The authors declare that no competing interests exist.
  9. M Azim Surani

    Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    a.surani@gurdon.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8640-4318

Funding

Wellcome (96738)

  • Yun Huang
  • Dang Vinh Do
  • Caroline Lee
  • Christopher A Penfold
  • Jan J Zylicz
  • Jamie A Hackett
  • M Azim Surani

Wellcome (92096)

  • Yun Huang
  • Dang Vinh Do
  • Caroline Lee
  • Christopher A Penfold
  • Jan J Zylicz
  • Jamie A Hackett
  • M Azim Surani

Cancer Research UK (C6946/A14492)

  • Yun Huang
  • Dang Vinh Do
  • Caroline Lee
  • Christopher A Penfold
  • Jan J Zylicz
  • Jamie A Hackett
  • M Azim Surani

European Molecular Biology Laboratory

  • Jong Kyoung Kim
  • John C Marioni

Cancer Research UK

  • Jong Kyoung Kim
  • John C Marioni

James Baird Fund, University of Cambridge

  • Yun Huang

DGIST Start-up Fund of the Ministry of Science, ICT and Future Planning (2017010073)

  • Jong Kyoung Kim

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 husbandry and experiments involving mice were authorized by a UK Home Office Project License 80/2637 and carried out in a Home Office-designated facility.

Copyright

© 2017, Huang 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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  1. Yun Huang
  2. Jong Kyoung Kim
  3. Dang Vinh Do
  4. Caroline Lee
  5. Christopher A Penfold
  6. Jan J Zylicz
  7. John C Marioni
  8. Jamie A Hackett
  9. M Azim Surani
(2017)
STELLA modulates transcriptional and endogenous retrovirus programs during maternal-to-zygotic transition
eLife 6:e22345.
https://doi.org/10.7554/eLife.22345

Share this article

https://doi.org/10.7554/eLife.22345

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