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LINE-1 Evasion of Epigenetic Repression in Humans

Sanchez-Luque, Francisco J ; Kempen, Marie-Jeanne H C ; Gerdes, Patricia LU orcid ; Vargas-Landin, Dulce B ; Richardson, Sandra R ; Troskie, Robin-Lee ; Jesuadian, J Samuel ; Cheetham, Seth W ; Carreira, Patricia E and Salvador-Palomeque, Carmen , et al. (2019) In Molecular Cell 75(3). p.12-604
Abstract

Epigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 24 hippocampal neurons with three distinct single-cell genomic approaches, we characterized and validated a somatic L1 insertion bearing a 3' transduction. The source (donor) L1 for this insertion was slightly 5' truncated, lacked the YY1 binding site, and was highly mobile when tested in vitro. Locus-specific bisulfite sequencing revealed that... (More)

Epigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 24 hippocampal neurons with three distinct single-cell genomic approaches, we characterized and validated a somatic L1 insertion bearing a 3' transduction. The source (donor) L1 for this insertion was slightly 5' truncated, lacked the YY1 binding site, and was highly mobile when tested in vitro. Locus-specific bisulfite sequencing revealed that the donor L1 and other young L1s with mutated YY1 binding sites were hypomethylated in embryonic stem cells, during neurodifferentiation, and in liver and brain tissue. These results explain how L1 can evade repression and retrotranspose in the human body.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Binding Sites/genetics, DNA Methylation/genetics, DNA-Binding Proteins/genetics, Epigenetic Repression/genetics, Genome, Human/genetics, Hippocampus/metabolism, Humans, Liver/metabolism, Long Interspersed Nucleotide Elements/genetics, Neurons/metabolism, Retroelements/genetics, Single-Cell Analysis, YY1 Transcription Factor/genetics
in
Molecular Cell
volume
75
issue
3
pages
12 - 604
publisher
Cell Press
external identifiers
  • scopus:85071350121
  • pmid:31230816
ISSN
1097-4164
DOI
10.1016/j.molcel.2019.05.024
language
English
LU publication?
no
additional info
Copyright © 2019 Elsevier Inc. All rights reserved.
id
4c61d179-3af9-4ddc-940d-87d615698ab7
date added to LUP
2024-06-10 16:09:50
date last changed
2024-11-26 22:15:01
@article{4c61d179-3af9-4ddc-940d-87d615698ab7,
  abstract     = {{<p>Epigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 24 hippocampal neurons with three distinct single-cell genomic approaches, we characterized and validated a somatic L1 insertion bearing a 3' transduction. The source (donor) L1 for this insertion was slightly 5' truncated, lacked the YY1 binding site, and was highly mobile when tested in vitro. Locus-specific bisulfite sequencing revealed that the donor L1 and other young L1s with mutated YY1 binding sites were hypomethylated in embryonic stem cells, during neurodifferentiation, and in liver and brain tissue. These results explain how L1 can evade repression and retrotranspose in the human body.</p>}},
  author       = {{Sanchez-Luque, Francisco J and Kempen, Marie-Jeanne H C and Gerdes, Patricia and Vargas-Landin, Dulce B and Richardson, Sandra R and Troskie, Robin-Lee and Jesuadian, J Samuel and Cheetham, Seth W and Carreira, Patricia E and Salvador-Palomeque, Carmen and García-Cañadas, Marta and Muñoz-Lopez, Martin and Sanchez, Laura and Lundberg, Mischa and Macia, Angela and Heras, Sara R and Brennan, Paul M and Lister, Ryan and Garcia-Perez, Jose L and Ewing, Adam D and Faulkner, Geoffrey J}},
  issn         = {{1097-4164}},
  keywords     = {{Binding Sites/genetics; DNA Methylation/genetics; DNA-Binding Proteins/genetics; Epigenetic Repression/genetics; Genome, Human/genetics; Hippocampus/metabolism; Humans; Liver/metabolism; Long Interspersed Nucleotide Elements/genetics; Neurons/metabolism; Retroelements/genetics; Single-Cell Analysis; YY1 Transcription Factor/genetics}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{3}},
  pages        = {{12--604}},
  publisher    = {{Cell Press}},
  series       = {{Molecular Cell}},
  title        = {{LINE-1 Evasion of Epigenetic Repression in Humans}},
  url          = {{http://dx.doi.org/10.1016/j.molcel.2019.05.024}},
  doi          = {{10.1016/j.molcel.2019.05.024}},
  volume       = {{75}},
  year         = {{2019}},
}