Journal
MOLECULAR CELL
Volume 74, Issue 3, Pages 555-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2019.02.036
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Funding
- Fondation pour la Recherche Medicale [FRM-DEP20131128533]
- European Research Council [ERC-2009-StG 243312]
- Agence Nationale de la Recherche (LABEX SIGNALIFE) [ANR-11-LABX-0028-01]
- Agence Nationale de la Recherche (RETROMET) [ANR-16-CE12-0020]
- Canceropole PACA (Projet Emergence)
- CNRS [GDR 3546]
- University Hospital Federation (FHU) OncoAge
- FEDER
- Inserm
- Universite Cote d'Azur (France)
- University of Dhaka (Bangladesh)
- Agence Nationale de la Recherche (RETROGENO) [ANR-12-BSV6-0003]
- Region Provence Alpes Cote d'Azur
- Conseil Departemental 06
- ITMO Cancer Aviesan [plan cancer]
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L1 retrotransposons are transposable elements and major contributors of genetic variation in humans. Where L1 integrates into the genome can directly impact human evolution and disease. Here, we experimentally induced L1 retrotransposition in cells and mapped integration sites at nucleotide resolution. At local scales, L1 integration is mostly restricted by genome sequence biases and the specificity of the L1 machinery. At regional scales, L1 shows a broad capacity for integration into all chromatin states, in contrast to other known mobile genetic elements. However, integration is influenced by the replication timing of target regions, suggesting a link to host DNA replication. The distribution of new L1 integrations differs from those of preexisting L1 copies, which are significantly reshaped by natural selection. Our findings reveal that the L1 machinery has evolved to efficiently target all genomic regions and underline a predominant role for post-integrative processes on the distribution of endogenous L1 elements.
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