Cargando…

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

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. Locu...

Descripción completa

Detalles Bibliográficos
Autores principales: Gerdes, Patricia, Chan, Dorothy, Lundberg, Mischa, Sanchez-Luque, Francisco J., Bodea, Gabriela O., Ewing, Adam D., Faulkner, Geoffrey J., Richardson, Sandra R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620060/
https://www.ncbi.nlm.nih.gov/pubmed/37798118
http://dx.doi.org/10.1101/gr.278003.123
_version_ 1785130123567038464
author Gerdes, Patricia
Chan, Dorothy
Lundberg, Mischa
Sanchez-Luque, Francisco J.
Bodea, Gabriela O.
Ewing, Adam D.
Faulkner, Geoffrey J.
Richardson, Sandra R.
author_facet Gerdes, Patricia
Chan, Dorothy
Lundberg, Mischa
Sanchez-Luque, Francisco J.
Bodea, Gabriela O.
Ewing, Adam D.
Faulkner, Geoffrey J.
Richardson, Sandra R.
author_sort Gerdes, Patricia
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10620060
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-106200602023-11-02 Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development Gerdes, Patricia Chan, Dorothy Lundberg, Mischa Sanchez-Luque, Francisco J. Bodea, Gabriela O. Ewing, Adam D. Faulkner, Geoffrey J. Richardson, Sandra R. Genome Res Research 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. Cold Spring Harbor Laboratory Press 2023-09 /pmc/articles/PMC10620060/ /pubmed/37798118 http://dx.doi.org/10.1101/gr.278003.123 Text en © 2023 Gerdes et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by/4.0/This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Gerdes, Patricia
Chan, Dorothy
Lundberg, Mischa
Sanchez-Luque, Francisco J.
Bodea, Gabriela O.
Ewing, Adam D.
Faulkner, Geoffrey J.
Richardson, Sandra R.
Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development
title Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development
title_full Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development
title_fullStr Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development
title_full_unstemmed Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development
title_short Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development
title_sort locus-resolution analysis of l1 regulation and retrotransposition potential in mouse embryonic development
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620060/
https://www.ncbi.nlm.nih.gov/pubmed/37798118
http://dx.doi.org/10.1101/gr.278003.123
work_keys_str_mv AT gerdespatricia locusresolutionanalysisofl1regulationandretrotranspositionpotentialinmouseembryonicdevelopment
AT chandorothy locusresolutionanalysisofl1regulationandretrotranspositionpotentialinmouseembryonicdevelopment
AT lundbergmischa locusresolutionanalysisofl1regulationandretrotranspositionpotentialinmouseembryonicdevelopment
AT sanchezluquefranciscoj locusresolutionanalysisofl1regulationandretrotranspositionpotentialinmouseembryonicdevelopment
AT bodeagabrielao locusresolutionanalysisofl1regulationandretrotranspositionpotentialinmouseembryonicdevelopment
AT ewingadamd locusresolutionanalysisofl1regulationandretrotranspositionpotentialinmouseembryonicdevelopment
AT faulknergeoffreyj locusresolutionanalysisofl1regulationandretrotranspositionpotentialinmouseembryonicdevelopment
AT richardsonsandrar locusresolutionanalysisofl1regulationandretrotranspositionpotentialinmouseembryonicdevelopment