A spontaneous genetically-induced epiallele at a retrotransposon shapes host genome function
- University of Cambridge, United Kingdom
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) recently formed in the inbred C57BL/6J mouse strain. In contrast to the C57BL/6J full-length IAP at this locus (Iap5-1full), Iap5-1solo 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. Iap5-1solo 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.
Data availability
Sequencing data have been deposited in GenBank under accession number MW308129. GEO accession codes for publicly available ChIP-seq datasets analysed in this study are listed is Supplementary Table 5.
Article and author information
Author details
Anne C Ferguson-Smith
Funding
Wellcome Trust (210757/Z/18/Z)
- Anne C Ferguson-Smith
Medical Research Council (MR/R009791/1)
- Anne C Ferguson-Smith
Biotechnology and Biological Sciences Research Council (BB/R009996/1)
- Anne C Ferguson-Smith
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Mouse work was carried out in accordance with the Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012 following ethical review by the University of Cambridge Animal Welfare and Ethical Review Body (Home Office project license # PC213320E).
Copyright
© 2021, Bertozzi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A spontaneous genetically-induced epiallele at a retrotransposon shapes host genome function
eLife 10:e65233.
https://doi.org/10.7554/eLife.65233
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