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Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development

Gerdes, Patricia LU orcid ; Chan, Dorothy ; Lundberg, Mischa ; Sanchez-Luque, Francisco J ; Bodea, Gabriela O ; Ewing, Adam D ; Faulkner, Geoffrey J and Richardson, Sandra R (2023) In Genome Research 33(9). p.1465-1481
Abstract

Mice harbor ∼2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity of an L1 copy is defined by both its sequence integrity and epigenetic status, including DNA methylation of the monomeric units constituting young mouse L1 promoters. Locus-specific L1 methylation dynamics during development may therefore elucidate and explain spatiotemporal niches of endogenous retrotransposition but remain unresolved. Here, we interrogate the retrotransposition efficiency and epigenetic fate of source (donor) L1s, identified as mobile in vivo. We show that promoter monomer loss consistently attenuates the relative retrotransposition potential of their offspring (daughter) L1 insertions. We... (More)

Mice harbor ∼2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity of an L1 copy is defined by both its sequence integrity and epigenetic status, including DNA methylation of the monomeric units constituting young mouse L1 promoters. Locus-specific L1 methylation dynamics during development may therefore elucidate and explain spatiotemporal niches of endogenous retrotransposition but remain unresolved. Here, we interrogate the retrotransposition efficiency and epigenetic fate of source (donor) L1s, identified as mobile in vivo. We show that promoter monomer loss consistently attenuates the relative retrotransposition potential of their offspring (daughter) L1 insertions. We also observe that most donor/daughter L1 pairs are efficiently methylated upon differentiation in vivo and in vitro. We use Oxford Nanopore Technologies (ONT) long-read sequencing to resolve L1 methylation genome-wide and at individual L1 loci, revealing a distinctive "smile" pattern in methylation levels across the L1 promoter region. Using Pacific Biosciences (PacBio) SMRT sequencing of L1 5' RACE products, we then examine DNA methylation dynamics at the mouse L1 promoter in parallel with transcription start site (TSS) distribution at locus-specific resolution. Together, our results offer a novel perspective on the interplay between epigenetic repression, L1 evolution, and genome stability.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Mice, Animals, Embryonic Development, Long Interspersed Nucleotide Elements, Retroelements/genetics, DNA Methylation, Promoter Regions, Genetic
in
Genome Research
volume
33
issue
9
pages
1465 - 1481
publisher
Cold Spring Harbor Laboratory Press (CSHL)
external identifiers
  • pmid:37798118
  • scopus:85174548113
ISSN
1549-5469
DOI
10.1101/gr.278003.123
language
English
LU publication?
no
additional info
© 2023 Gerdes et al.; Published by Cold Spring Harbor Laboratory Press.
id
d4ae86da-df55-4b9f-b670-2f68befa1cff
date added to LUP
2024-06-10 15:12:22
date last changed
2024-06-11 04:01:15
@article{d4ae86da-df55-4b9f-b670-2f68befa1cff,
  abstract     = {{<p>Mice harbor ∼2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity of an L1 copy is defined by both its sequence integrity and epigenetic status, including DNA methylation of the monomeric units constituting young mouse L1 promoters. Locus-specific L1 methylation dynamics during development may therefore elucidate and explain spatiotemporal niches of endogenous retrotransposition but remain unresolved. Here, we interrogate the retrotransposition efficiency and epigenetic fate of source (donor) L1s, identified as mobile in vivo. We show that promoter monomer loss consistently attenuates the relative retrotransposition potential of their offspring (daughter) L1 insertions. We also observe that most donor/daughter L1 pairs are efficiently methylated upon differentiation in vivo and in vitro. We use Oxford Nanopore Technologies (ONT) long-read sequencing to resolve L1 methylation genome-wide and at individual L1 loci, revealing a distinctive "smile" pattern in methylation levels across the L1 promoter region. Using Pacific Biosciences (PacBio) SMRT sequencing of L1 5' RACE products, we then examine DNA methylation dynamics at the mouse L1 promoter in parallel with transcription start site (TSS) distribution at locus-specific resolution. Together, our results offer a novel perspective on the interplay between epigenetic repression, L1 evolution, and genome stability.</p>}},
  author       = {{Gerdes, Patricia and Chan, Dorothy and Lundberg, Mischa and Sanchez-Luque, Francisco J and Bodea, Gabriela O and Ewing, Adam D and Faulkner, Geoffrey J and Richardson, Sandra R}},
  issn         = {{1549-5469}},
  keywords     = {{Mice; Animals; Embryonic Development; Long Interspersed Nucleotide Elements; Retroelements/genetics; DNA Methylation; Promoter Regions, Genetic}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1465--1481}},
  publisher    = {{Cold Spring Harbor Laboratory Press (CSHL)}},
  series       = {{Genome Research}},
  title        = {{Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development}},
  url          = {{http://dx.doi.org/10.1101/gr.278003.123}},
  doi          = {{10.1101/gr.278003.123}},
  volume       = {{33}},
  year         = {{2023}},
}