Epigenetic changes induced by in utero dietary challenge result in phenotypic variability in successive generations of mice.
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Authors
Galvão, António M
Millership, Steven J
To, Wilson
Prodani, Chiara
McNamara, Gráinne
Bruno, Ludovica
Sardini, Alessandro
Webster, Zoe
McGinty, James
French, Paul M W
Watkinson, William
Publication Date
2022-05-05Journal Title
Nature communications
ISSN
2041-1723
Volume
13
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Van de Pette, M., Dimond, A., Galvão, A. M., Millership, S. J., To, W., Prodani, C., McNamara, G., et al. (2022). Epigenetic changes induced by in utero dietary challenge result in phenotypic variability in successive generations of mice.. Nature communications, 13 (1) https://doi.org/10.1038/s41467-022-30022-2
Abstract
Transmission of epigenetic information between generations occurs in nematodes, flies and plants, mediated by specialised small RNA pathways, modified histones and DNA methylation. Similar processes in mammals can also affect phenotype through intergenerational or trans-generational mechanisms. Here we generate a luciferase knock-in reporter mouse for the imprinted Dlk1 locus to visualise and track epigenetic fidelity across generations. Exposure to high-fat diet in pregnancy provokes sustained re-expression of the normally silent maternal Dlk1 in offspring (loss of imprinting) and increased DNA methylation at the somatic differentially methylated region (sDMR). In the next generation heterogeneous Dlk1 mis-expression is seen exclusively among animals born to F1-exposed females. Oocytes from these females show altered gene and microRNA expression without changes in DNA methylation, and correct imprinting is restored in subsequent generations. Our results illustrate how diet impacts the foetal epigenome, disturbing canonical and non-canonical imprinting mechanisms to modulate the properties of successive generations of offspring.
Keywords
Animals, Mammals, Mice, DNA Methylation, Epigenesis, Genetic, Genomic Imprinting, Pregnancy, Female, Diet, High-Fat, Biological Variation, Population
Sponsorship
Medical Research Council (MC_U120027516, MR/S000437/1, MC_UP_1605/12, MC_UP_1605/11)
Wellcome Trust (ISSF PS3125_WCMA, 099276/Z/12/Z)
Biotechnology and Biological Sciences Research Council (BB/P002307/1, BBS/E/B/000C0423, BB/P008623/1)
Identifiers
35513363, PMC9072353
External DOI: https://doi.org/10.1038/s41467-022-30022-2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337839
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