Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

DEVELOPMENT

Retrotransposing a promoter for development

Nature Cell Biology volume 23, pages 1221–1223 (2021)Cite this article

Subjects

Formerly regarded as ‘junk’ DNA, transposable elements are now thought to be players in genome evolution. A new study reveals remarkable conservation of a retrotransposon insertion acting as an alternative promoter to drive the expression of a cell cycle regulator isoform in early embryos, potentially controlling the timing of pre-implantation development.

More than 40% of our genomes are composed of mobile genetic elements and their remnants, collectively referred to as transposable elements (TEs) that have colonized our genomes in part due to their capacity to replicate independently from the host genome. TEs were discovered around 75 years ago and derive primarily from ancient retroviruses that have become endogenous in our genomes through a ‘copy-and-paste’ mechanism. Interestingly, long-terminal repeat (LTR) sequences, which are regulatory regions surrounding endogenous retroviruses (ERVs), harbour RNA polymerase II promoters and transcription factor binding sites1. This has led to the view that TEs may play a role in genome regulation2,3. However, approximately 10% of spontaneously de novo mutations in mice are attributable to TEs, and multiple diseases including cancer show a significant increase in TE expression and notably ERV transcription4. To counteract such potential deleterious effects, the host has developed a series of defence mechanisms to avoid TE activity, including its transcription. However, in a race between host and parasites, it is thought that TEs not only act as regulatory elements to rewire host transcriptional circuitries, but also expand transcript diversity through modifications of donor–acceptor splicing sequences5. A notable example of transcript diversity occurs in mouse oocytes, where an oocyte-specific isoform of the endoribonuclease DICER is generated through the activity of an intronic ERV6. However, due to the diverse genomic integrations of TEs, TE-mediated gene-regulation activities have in general been thought of as non-essential and species-specific. In the last issue of Cell, Modzelewski and Shao et al. report that a retrotransposon drives the expression of a specific isoform of a cell cycle regulator, the cyclin-dependent kinase 2-associated protein 1 (Cdk2ap1). This is a striking finding as this isoform is not only essential for mouse development, but it is actually conserved in humans and regulates the pre-implantation duration in mammals7. Thus, these findings provide exciting evidence that TE insertions can regulate the expression of conserved proteins with an essential function, highlighting a remarkable evolutionary and fine-regulatory genome function.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: A retrotransposon drives expression of an isoform of the cell cycle regulator Cdk2ap1.

References

  1. Kunarso, G. et al. Nat. Genet. 42, 631–634 (2010).

    Article  CAS  Google Scholar 

  2. Bejerano, G. et al. Nature 441, 87–90 (2006).

    Article  CAS  Google Scholar 

  3. Chuong, E. B. et al. Nat. Genet. 45, 325–329 (2013).

    Article  CAS  Google Scholar 

  4. Iskow, R. C. et al. Cell 141, 1253–1261 (2010).

    Article  CAS  Google Scholar 

  5. Cosby, R. L., Chang, N. & Feschotte, C. Genes Dev. 33, 1098–1116 (2019).

    Article  CAS  Google Scholar 

  6. Flemr, M. et al. Cell 155, 807 (2013).

    Article  CAS  Google Scholar 

  7. Modzelewski, A. J. et al. Cell 184, 5541–5558 (2021).

    Article  CAS  Google Scholar 

  8. Peaston, A. E. et al. Dev. Cell 7, 597–606 (2004).

    Article  CAS  Google Scholar 

  9. Göcke, J. et al. Cell Stem Cell 16, 135–141 (2015).

    Article  Google Scholar 

  10. Fadloun, A. et al. Nat. Struct. Mol. Biol. 20, 332–338 (2013).

    Article  CAS  Google Scholar 

  11. Jachowicz, J. W. et al. Nat. Genet. 49, 1502–1510 (2017).

    Article  CAS  Google Scholar 

  12. Percharde, M. et al. Cell 174, 391–405 (2018).

    Article  CAS  Google Scholar 

  13. Hendrickson, P. G. et al. Nat. Genet. 49, 925–934 (2017).

    Article  CAS  Google Scholar 

  14. Shintani, S. et al. Mol. Cell. Biol. 20, 6300–6307 (2000).

    Article  CAS  Google Scholar 

  15. Singh, P. et al. Development 146, dev180273 (2019).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, München, Germany

    Antoine Canat & Maria-Elena Torres-Padilla

  2. Faculty of Biology, Ludwig-Maximilians Universität, München, Germany

    Maria-Elena Torres-Padilla

Authors
  1. Antoine Canat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria-Elena Torres-Padilla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria-Elena Torres-Padilla.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Canat, A., Torres-Padilla, ME. Retrotransposing a promoter for development. Nat Cell Biol 23, 1221–1223 (2021). https://doi.org/10.1038/s41556-021-00806-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41556-021-00806-7

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing