Heritable L1 retrotransposition in the mouse primordial germline and early embryo
(2017) In Genome Research 27(8). p.1395-1405- Abstract
LINE-1 (L1) retrotransposons are a noted source of genetic diversity and disease in mammals. To expand its genomic footprint, L1 must mobilize in cells that will contribute their genetic material to subsequent generations. Heritable L1 insertions may therefore arise in germ cells and in pluripotent embryonic cells, prior to germline specification, yet the frequency and predominant developmental timing of such events remain unclear. Here, we applied mouse retrotransposon capture sequencing (mRC-seq) and whole-genome sequencing (WGS) to pedigrees of C57BL/6J animals, and uncovered an L1 insertion rate of ≥1 event per eight births. We traced heritable L1 insertions to pluripotent embryonic cells and, strikingly, to early primordial germ... (More)
LINE-1 (L1) retrotransposons are a noted source of genetic diversity and disease in mammals. To expand its genomic footprint, L1 must mobilize in cells that will contribute their genetic material to subsequent generations. Heritable L1 insertions may therefore arise in germ cells and in pluripotent embryonic cells, prior to germline specification, yet the frequency and predominant developmental timing of such events remain unclear. Here, we applied mouse retrotransposon capture sequencing (mRC-seq) and whole-genome sequencing (WGS) to pedigrees of C57BL/6J animals, and uncovered an L1 insertion rate of ≥1 event per eight births. We traced heritable L1 insertions to pluripotent embryonic cells and, strikingly, to early primordial germ cells (PGCs). New L1 insertions bore structural hallmarks of target-site primed reverse transcription (TPRT) and mobilized efficiently in a cultured cell retrotransposition assay. Together, our results highlight the rate and evolutionary impact of heritable L1 retrotransposition and reveal retrotransposition-mediated genomic diversification as a fundamental property of pluripotent embryonic cells in vivo.
(Less)
- author
- publishing date
- 2017-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Embryo, Mammalian/cytology, Female, Genomics/methods, Germ Cells, HeLa Cells, Humans, Long Interspersed Nucleotide Elements, Male, Mice, Mice, Inbred C57BL, Mosaicism, Whole Genome Sequencing/methods
- in
- Genome Research
- volume
- 27
- issue
- 8
- pages
- 1395 - 1405
- publisher
- Cold Spring Harbor Laboratory Press (CSHL)
- external identifiers
-
- pmid:28483779
- scopus:85026639648
- ISSN
- 1549-5469
- DOI
- 10.1101/gr.219022.116
- language
- English
- LU publication?
- no
- additional info
- © 2017 Richardson et al.; Published by Cold Spring Harbor Laboratory Press.
- id
- 2344c88f-7088-4c11-8928-cc0c6d324b68
- date added to LUP
- 2024-06-10 16:13:14
- date last changed
- 2024-06-12 03:06:28
@article{2344c88f-7088-4c11-8928-cc0c6d324b68, abstract = {{<p>LINE-1 (L1) retrotransposons are a noted source of genetic diversity and disease in mammals. To expand its genomic footprint, L1 must mobilize in cells that will contribute their genetic material to subsequent generations. Heritable L1 insertions may therefore arise in germ cells and in pluripotent embryonic cells, prior to germline specification, yet the frequency and predominant developmental timing of such events remain unclear. Here, we applied mouse retrotransposon capture sequencing (mRC-seq) and whole-genome sequencing (WGS) to pedigrees of C57BL/6J animals, and uncovered an L1 insertion rate of ≥1 event per eight births. We traced heritable L1 insertions to pluripotent embryonic cells and, strikingly, to early primordial germ cells (PGCs). New L1 insertions bore structural hallmarks of target-site primed reverse transcription (TPRT) and mobilized efficiently in a cultured cell retrotransposition assay. Together, our results highlight the rate and evolutionary impact of heritable L1 retrotransposition and reveal retrotransposition-mediated genomic diversification as a fundamental property of pluripotent embryonic cells in vivo.</p>}}, author = {{Richardson, Sandra R and Gerdes, Patricia and Gerhardt, Daniel J and Sanchez-Luque, Francisco J and Bodea, Gabriela-Oana and Muñoz-Lopez, Martin and Jesuadian, J Samuel and Kempen, Marie-Jeanne H C and Carreira, Patricia E and Jeddeloh, Jeffrey A and Garcia-Perez, Jose L and Kazazian, Haig H and Ewing, Adam D and Faulkner, Geoffrey J}}, issn = {{1549-5469}}, keywords = {{Animals; Embryo, Mammalian/cytology; Female; Genomics/methods; Germ Cells; HeLa Cells; Humans; Long Interspersed Nucleotide Elements; Male; Mice; Mice, Inbred C57BL; Mosaicism; Whole Genome Sequencing/methods}}, language = {{eng}}, number = {{8}}, pages = {{1395--1405}}, publisher = {{Cold Spring Harbor Laboratory Press (CSHL)}}, series = {{Genome Research}}, title = {{Heritable L1 retrotransposition in the mouse primordial germline and early embryo}}, url = {{http://dx.doi.org/10.1101/gr.219022.116}}, doi = {{10.1101/gr.219022.116}}, volume = {{27}}, year = {{2017}}, }