G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst
- University of Cambridge, United Kingdom
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.
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G9a regulates temporal preimplantation developmental program and lineage segregation in blastocystPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE106790).
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Global Deterministic and Stochastic Allelic Specific Gene Expression in Single Blastomeres of Mouse Early EmbryosPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE22182).
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The landscape of accessible chromatin in mammalian pre-implantation embryos (RNA-Seq)Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE66582).
Article and author information
Author details
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.
Reviewing Editor
- Asifa Akhtar, Max Planck Institute for Immunobiology and Epigenetics, Germany
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.
Version history
- Received: November 14, 2017
- Accepted: May 9, 2018
- Accepted Manuscript published: May 10, 2018 (version 1)
- 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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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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