STELLA modulates transcriptional and endogenous retrovirus programs during maternal-to-zygotic transition
- University of Cambridge, United Kingdom
- Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea
- European Molecular Biology Laboratory - European Bioinformatics Institute, United Kingdom
- 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.
Data availability
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DBTMEE: a database of transcriptome in mouse early embryosPublicly available to download from URL.
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2C::tomato ES cells, 2-cell embryos and wild type oocytesPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE33923).
Article and author information
Author details
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.
Reviewing Editor
- Robb Krumlauf, Stowers Institute for Medical Research, United States
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.
Version history
- Received: October 18, 2016
- Accepted: March 9, 2017
- Accepted Manuscript published: March 21, 2017 (version 1)
- Version of Record published: April 25, 2017 (version 2)
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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STELLA modulates transcriptional and endogenous retrovirus programs during maternal-to-zygotic transition
eLife 6:e22345.
https://doi.org/10.7554/eLife.22345
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