title: Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci.
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.
authors.affiliation: INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France.|Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France.|FHU OncoAge, University of Nice-Sophia Antipolis, Nice, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Philippe
authors.affiliation: INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France.|Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France.|Ecole Normale Supérieure, Paris, France.
authors.forename: Dulce B
authors.identifier: 0000-0002-4773-9406
authors.initials: DB
authors.lastname: Vargas-Landin
authors.affiliation: INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France.|Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France.|FHU OncoAge, University of Nice-Sophia Antipolis, Nice, France.
authors.forename: Aurélien J
authors.identifier: 0000-0001-7221-4874
authors.initials: AJ
authors.lastname: Doucet
authors.affiliation: INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France.|Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France.
authors.forename: Dominic
authors.initials: D
authors.lastname: van Essen
authors.affiliation: INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France.|Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France.
authors.forename: Jorge
authors.identifier: 0000-0003-2547-4213
authors.initials: J
authors.lastname: Vera-Otarola
authors.affiliation: INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France.|Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France.|Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Monika
authors.initials: M
authors.lastname: Kuciak
authors.affiliation: Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Corbin
authors.affiliation: INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France.|Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France.
authors.forename: Pilvi
authors.initials: P
authors.lastname: Nigumann
authors.affiliation: INSERM U1081, CNRS UMR 7284, Institute for Research on Cancer and Aging of Nice, Nice, France.|Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France.|FHU OncoAge, University of Nice-Sophia Antipolis, Nice, France.
authors.forename: Gaël
authors.identifier: 0000-0001-5620-3091
authors.initials: G
authors.lastname: Cristofari
mesh_terms: D002460:Cell Line; D044127:Epigenesis, Genetic; D056426:Genetic Loci; D006801:Humans; D018626:Retroelements; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D018626:Retroelements
keywords: DNA repeat; L1; LINE-1; chromosomes; evolutionary biology; genes; genome instability; genomics; human; mobile genetic element; repetitive DNA; retroelement; retrotransposition; retrotransposon; transposable elements; transposon