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.
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.
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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Meiotic crossover recombination is essential for both accurate chromosome segregation and the generation of new haplotypes for natural selection to act upon. This requirement is known as crossover assurance and is one example of crossover control. While the conserved role of the ATPase, PCH-2, during meiotic prophase has been enigmatic, a universal phenotype when pch-2 or its orthologs are mutated is a change in the number and distribution of meiotic crossovers. Here, we show that PCH-2 controls the number and distribution of crossovers by antagonizing their formation. This antagonism produces different effects at different stages of meiotic prophase: early in meiotic prophase, PCH-2 prevents double-strand breaks from becoming crossover-eligible intermediates, limiting crossover formation at sites of initial double-strand break formation and homolog interactions. Later in meiotic prophase, PCH-2 winnows the number of crossover-eligible intermediates, contributing to the designation of crossovers and ultimately, crossover assurance. We also demonstrate that PCH-2 accomplishes this regulation through the meiotic HORMAD, HIM-3. Our data strongly support a model in which PCH-2’s conserved role is to remodel meiotic HORMADs throughout meiotic prophase to destabilize crossover-eligible precursors and coordinate meiotic recombination with synapsis, ensuring the progressive implementation of meiotic recombination and explaining its function in the pachytene checkpoint and crossover control.
