Functional evaluation of transposable elements as enhancers in mouse embryonic and trophoblast stem cells

  1. Christopher D Todd
  2. Özgen Deniz
  3. Darren Taylor
  4. Miguel R Branco  Is a corresponding author
  1. Queen Mary University of London, United Kingdom

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.

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

Article and author information

Author details

  1. Christopher D Todd

    Blizard Institute, Queen Mary University of London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Özgen Deniz

    Blizard Institute, Queen Mary University of London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Darren Taylor

    Blizard Institute, Queen Mary University of London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Miguel R Branco

    Blizard Institute, Queen Mary University of London, London, United Kingdom
    For correspondence
    m.branco@qmul.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9447-1548

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.

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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  1. Christopher D Todd
  2. Özgen Deniz
  3. Darren Taylor
  4. Miguel R Branco
(2019)
Functional evaluation of transposable elements as enhancers in mouse embryonic and trophoblast stem cells
eLife 8:e44344.
https://doi.org/10.7554/eLife.44344

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https://doi.org/10.7554/eLife.44344