Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci

  1. Claude Philippe
  2. Dulce B Vargas-Landin
  3. Aurelien J Doucet
  4. Dominic van Essen
  5. Jorge Vera-Otarola
  6. Monika Kuciak
  7. Antoine Corbin
  8. Pilvi Nigumann
  9. Gaël Cristofari  Is a corresponding author
  1. Institute for Research on Cancer and Aging of Nice, France
  2. Institute for Research on Cancer and Aging of Nice, INSERM U1081, CNRS UMR 7284, University of Nice-Sophia-Antipolis, France
  3. 1Institute for Research on Cancer and Aging of Nice, France
  4. Ecole Normale Supérieure de Lyon, France

Abstract

LINE-1 (L1) retrotransposons represent approximately one sixth of the human genome, but only the human-specific L1HS-Ta subfamily acts as an endogenous mutagen in modern humans, reshaping both somatic and germline genomes. Due to their high levels of sequence identity and the existence of many polymorphic insertions absent from the reference genome, the transcriptional activation of individual genomic L1HS-Ta copies remains poorly understood. Here we comprehensively mapped fixed and polymorphic L1HS-Ta copies in 12 commonly-used somatic cell lines, and identified transcriptional and epigenetic signatures allowing the unambiguous identification of active L1HS-Ta copies in their genomic context. Strikingly, only a very restricted subset of L1HS-Ta loci - some being polymorphic among individuals - significantly contributes to the bulk of L1 expression, and these loci are differentially regulated among distinct cell lines. Thus, our data support a local model of L1 transcriptional activation in somatic cells, governed by individual-, locus-, and cell-type-specific determinants.

Article and author information

Author details

  1. Claude Philippe

    INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Dulce B Vargas-Landin

    INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Aurelien J Doucet

    Faculty of Medicine, Institute for Research on Cancer and Aging of Nice, INSERM U1081, CNRS UMR 7284, University of Nice-Sophia-Antipolis, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Dominic van Essen

    INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Jorge Vera-Otarola

    INSERM U1081, CNRS UMR 7284, 1Institute for Research on Cancer and Aging of Nice, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Monika Kuciak

    Faculty of Medicine, Institute for Research on Cancer and Aging of Nice, INSERM U1081, CNRS UMR 7284, University of Nice-Sophia-Antipolis, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Antoine Corbin

    Ecole Normale Supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Pilvi Nigumann

    INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Gaël Cristofari

    INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France
    For correspondence
    Gael.Cristofari@unice.fr
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Kathy Burns, McKusick-Nathans Institute of Genetic Medicine, United States

Version history

  1. Received: December 18, 2015
  2. Accepted: March 25, 2016
  3. Accepted Manuscript published: March 26, 2016 (version 1)
  4. Version of Record published: May 13, 2016 (version 2)

Copyright

© 2016, Philippe 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.

Metrics

  • 7,342
    views
  • 1,223
    downloads
  • 125
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Claude Philippe
  2. Dulce B Vargas-Landin
  3. Aurelien J Doucet
  4. Dominic van Essen
  5. Jorge Vera-Otarola
  6. Monika Kuciak
  7. Antoine Corbin
  8. Pilvi Nigumann
  9. Gaël Cristofari
(2016)
Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci
eLife 5:e13926.
https://doi.org/10.7554/eLife.13926

Share this article

https://doi.org/10.7554/eLife.13926

Further reading

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Lucie Crhak Khaitova, Pavlina Mikulkova ... Karel Riha
    Research Article

    Heat stress is a major threat to global crop production, and understanding its impact on plant fertility is crucial for developing climate-resilient crops. Despite the known negative effects of heat stress on plant reproduction, the underlying molecular mechanisms remain poorly understood. Here, we investigated the impact of elevated temperature on centromere structure and chromosome segregation during meiosis in Arabidopsis thaliana. Consistent with previous studies, heat stress leads to a decline in fertility and micronuclei formation in pollen mother cells. Our results reveal that elevated temperature causes a decrease in the amount of centromeric histone and the kinetochore protein BMF1 at meiotic centromeres with increasing temperature. Furthermore, we show that heat stress increases the duration of meiotic divisions and prolongs the activity of the spindle assembly checkpoint during meiosis I, indicating an impaired efficiency of the kinetochore attachments to spindle microtubules. Our analysis of mutants with reduced levels of centromeric histone suggests that weakened centromeres sensitize plants to elevated temperature, resulting in meiotic defects and reduced fertility even at moderate temperatures. These results indicate that the structure and functionality of meiotic centromeres in Arabidopsis are highly sensitive to heat stress, and suggest that centromeres and kinetochores may represent a critical bottleneck in plant adaptation to increasing temperatures.

    1. Chromosomes and Gene Expression
    Allison Coté, Aoife O'Farrell ... Arjun Raj
    Research Article

    Splicing is the stepwise molecular process by which introns are removed from pre-mRNA and exons are joined together to form mature mRNA sequences. The ordering and spatial distribution of these steps remain controversial, with opposing models suggesting splicing occurs either during or after transcription. We used single-molecule RNA FISH, expansion microscopy, and live-cell imaging to reveal the spatiotemporal distribution of nascent transcripts in mammalian cells. At super-resolution levels, we found that pre-mRNA formed clouds around the transcription site. These clouds indicate the existence of a transcription-site-proximal zone through which RNA move more slowly than in the nucleoplasm. Full-length pre-mRNA undergo continuous splicing as they move through this zone following transcription, suggesting a model in which splicing can occur post-transcriptionally but still within the proximity of the transcription site, thus seeming co-transcriptional by most assays. These results may unify conflicting reports of co-transcriptional versus post-transcriptional splicing.