G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

Abstract

Early mouse development is regulated and accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2). Previously, we provided insights into its role in post-implantation development (Zylicz et al., 2015). Here we explore the impact of depleting the maternally inherited G9a in oocytes on development shortly after fertilisation. We show that G9a accumulates typically at 4 to 8-cell stage to promote timely repression of a subset of 4-cell stage-specific genes. Loss of maternal inheritance of G9a disrupts the gene regulatory network resulting in developmental delay and destabilisation of inner cell mass lineages by the late blastocyst stage. Our results indicate a vital role of this maternally inherited epigenetic regulator in creating conducive conditions for developmental progression and on cell fate choices.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE106790.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. 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
  2. Maud Borensztein

    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:" 0000-0002-4378-5018
  3. Frederick CK Wong

    Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7843-9126
  5. 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.
  6. Sabine Dietmann

    Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. 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)

  • Jan J Zylicz
  • Maud Borensztein
  • Yun Huang
  • Caroline Lee
  • Sabine Dietmann
  • M Azim Surani

Wellcome (RG44593)

  • Jan J Zylicz

H2020 Marie Skłodowska-Curie Actions (706144)

  • Maud Borensztein

Cancer Research UK (C6946/A14492)

  • Jan J Zylicz
  • Maud Borensztein
  • Yun Huang
  • Caroline Lee
  • Sabine Dietmann
  • M Azim Surani

James Baird Fund, University of Cambridge

  • Yun Huang

Wellcome (92096)

  • Jan J Zylicz
  • Maud Borensztein
  • Yun Huang
  • Caroline Lee
  • Sabine Dietmann
  • M Azim Surani

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

Ethics

Animal experimentation: Animal experimentation: All husbandry and experiments involving mice were authorized by a UK Home Office Project Licenses 80/2637 and PE596D1FE and carried out in a Home Office-designated facility.

Reviewing Editor

  1. Asifa Akhtar, Max Planck Institute for Immunobiology and Epigenetics, Germany

Publication history

  1. Received: November 14, 2017
  2. Accepted: May 9, 2018
  3. Accepted Manuscript published: May 10, 2018 (version 1)
  4. Version of Record published: May 18, 2018 (version 2)

Copyright

© 2018, Zylicz 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. Jan J Zylicz
  2. Maud Borensztein
  3. Frederick CK Wong
  4. Yun Huang
  5. Caroline Lee
  6. Sabine Dietmann
  7. M Azim Surani
(2018)
G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst
eLife 7:e33361.
https://doi.org/10.7554/eLife.33361

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