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A spontaneous genetically-induced epiallele at a retrotransposon shapes host genome function

Published version
Peer-reviewed

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Authors

Bertozzi, Tessa 
Hanin, Geula 
Kazachenka, Anastasiya 
Ferguson-Smith, Anne  ORCID logo  https://orcid.org/0000-0003-4996-9990

Abstract

Intracisternal A-particles (IAPs) are endogenous retroviruses (ERVs) responsible for most insertional mutations in the mouse. Full-length IAPs harbour genes flanked by long terminal repeats (LTRs). Here, we identify a solo LTR IAP variant (Iap5-1solo 31 ) recently formed in the inbred C57BL/6J mouse strain. In contrast to the C57BL/6J full-length IAP at this locus (Iap5-1full), Iap5-1 solo lacks DNA methylation and H3K9 trimethylation. The distinct DNA methylation levels between the two alleles are established during preimplantation development, likely due to loss of KRAB zinc finger protein binding at the Iap5-1solo variant. Iap5-1 solo methylation increases and becomes more variable in a hybrid genetic background yet is unresponsive to maternal dietary methyl supplementation. Differential epigenetic modification of the two variants is associated with metabolic differences and tissue-specific changes in adjacent gene expression. Our characterisation of Iap5-1 as a genetically-induced epiallele with functional consequences establishes a new model to study transposable element repression and host-element co-evolution

Description

Keywords

DNA methylation, IAP, chromosomes, endogenous retrovirus, epiallele, gene expression, genetics, genomics, mouse, transposable element, Animals, DNA Methylation, Endogenous Retroviruses, Epigenesis, Genetic, Female, Gene Expression, Male, Mice, Mice, Inbred C57BL, Retroelements, Terminal Repeat Sequences, Zinc Fingers

Journal Title

eLife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

Publisher

eLife Sciences Publications Ltd
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/R009996/1)
Wellcome Trust (210757/Z/18/Z)
Medical Research Council (MR/R009791/1)
Biotechnology and Biological Sciences Research Council (BB/G020930/1)
MRC (MR/W003783/1)