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.

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  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

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