Epigenetic changes induced by in utero dietary challenge result in phenotypic variability in successive generations of mice
| Autor: | Mathew Van de Pette, Andrew Dimond, António M. Galvão, Steven J. Millership, Wilson To, Chiara Prodani, Gráinne McNamara, Ludovica Bruno, Alessandro Sardini, Zoe Webster, James McGinty, Paul M. W. French, Anthony G. Uren, Juan Castillo-Fernandez, William Watkinson, Anne C. Ferguson-Smith, Matthias Merkenschlager, Rosalind M. John, Gavin Kelsey, Amanda G. Fisher |
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| Přispěvatelé: | Van De Pette, Mathew [0000-0002-1423-5957], Dimond, Andrew [0000-0002-2996-2479], Uren, Anthony G [0000-0002-6019-7111], Castillo-Fernandez, Juan [0000-0002-0034-8029], Ferguson-Smith, Anne C [0000-0002-7608-5894], Merkenschlager, Matthias [0000-0003-2889-3288], Kelsey, Gavin [0000-0002-9762-5634], Fisher, Amanda G [0000-0003-3010-3644], Apollo - University of Cambridge Repository, Wellcome Trust, Medical Research Council (MRC), Van de Pette, Mathew [0000-0002-1423-5957] |
| Rok vydání: | 2022 |
| Předmět: |
EXPRESSION
HIGH-FAT DIET 631/136/2442 IMPRINTED GENES 49/23 45/88 General Physics and Astronomy MOUSE INHERITANCE Diet High-Fat 59/5 General Biochemistry Genetics and Molecular Biology Epigenesis Genetic ACTIVATION Genomic Imprinting Mice Pregnancy SPERM RNAS Animals NONCODING RNA 14/19 Mammals 45/91 Science & Technology Multidisciplinary DLK1 article 631/337/176/1968 631/337/176/1988 General Chemistry DNA Methylation 631/136/2434/1706 Multidisciplinary Sciences Biological Variation Population 13/51 631/1647/245/2222 Science & Technology - Other Topics Female 64/60 |
| Zdroj: | Nature Communications. 13 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-022-30022-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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