Functional evaluation of transposable elements as enhancers in mouse embryonic and trophoblast stem cells
Abstract
Transposable elements (TEs) are thought to have helped establish gene regulatory networks. Both the embryonic and extraembryonic lineages of the early mouse embryo have seemingly co-opted TEs as enhancers, but there is little evidence that they play significant roles in gene regulation. Here we tested a set of long terminal repeat TE families for roles as enhancers in mouse embryonic and trophoblast stem cells. Epigenomic and transcriptomic data suggested that a large number of TEs helped to establish tissue-specific gene expression programmes. Genetic editing of individual TEs confirmed a subset of these regulatory relationships. However, a wider survey via CRISPR interference of RLTR13D6 elements in embryonic stem cells revealed that only a minority play significant roles in gene regulation. Our results suggest that a subset of TEs are important for gene regulation in early mouse development, and highlight the importance of functional experiments when evaluating gene regulatory roles of TEs.
Data availability
Sequencing data have been deposited in GEO under accession code GSE122856.
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Article and author information
Author details
Funding
Wellcome (Sir Henry Dale Fellowship 101225/Z/13/Z)
- Miguel R Branco
The Medical College of Saint Bartholomew's Hospital Trust (Donald Hunter Studentship)
- Christopher D Todd
Biotechnology and Biological Sciences Research Council (BB/R505997/1)
- Darren Taylor
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Deborah Bourc'his, Institut Curie, France
Version history
- Received: December 12, 2018
- Accepted: April 20, 2019
- Accepted Manuscript published: April 23, 2019 (version 1)
- Version of Record published: May 31, 2019 (version 2)
- Version of Record updated: February 28, 2020 (version 3)
Copyright
© 2019, Todd 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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