@misc{10481/86042,
year = {2023},
month = {10},
url = {https://hdl.handle.net/10481/86042},
abstract = {Mice harbor similar to 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.},
organization = {European Union (EU)},
organization = {Australian Government
Department of Industry, Innovation and Science},
organization = {Mater Research Frank Clair Scholarship},
organization = {University of Queensland Research Training Program Scholarship},
organization = {Commonwealth Scientific and Industrial Research Organisation Postgraduate Top-Up Scholarship},
organization = {National Health and Medical Research Council (NHMRC) of Australia},
organization = {Australian Research Council
	GNT1108258},
organization = {National Health and Medical Research Council (NHMRC) of Australia GNT1125645, GNT1138795, GNT1173711, 	
	GNT1173476},
organization = {Australian Research Council
	DP200102919},
organization = {Australian Department of Health Medical Frontiers Future Fund
	MRF1175457},
organization = {Advance Queensland Women's Academic Fund Maternity Funding award},
organization = {Mater Foundation},
organization = {Australian Research Council
	LE130100078},
organization = {PIOF-GA-2013-623324},
publisher = {Cold Spring Harbor Laboratory Press},
title = {Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development},
doi = {10.1101/gr.278003.123},
author = {Gerdes, Patricia and Sánchez Luque, Francisco José},
}