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

Claude Philippe, Dulce Vargas Landin, Aurelien J. Doucet, Dominic van Essen, Jorge Vera-Otarola, Monika Kuciak, Antoine Corbin, Pilvi Nigumann, Gael Cristofari

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Abstract

© Philippe et al. 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.
Original languageEnglish
Article numbere13926
Pages (from-to)1-30
JournaleLife
Volume5
DOIs
Publication statusPublished - 26 Mar 2016
Externally publishedYes

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Philippe, C., Vargas Landin, D., Doucet, A. J., van Essen, D., Vera-Otarola, J., Kuciak, M., ... Cristofari, G. (2016). Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci. eLife, 5, 1-30. [e13926]. https://doi.org/10.7554/eLife.13926