Repository logo
 

Epigenetic changes induced by in utero dietary challenge result in phenotypic variability in successive generations of mice.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Van de Pette, Mathew  ORCID logo  https://orcid.org/0000-0002-1423-5957
Galvão, António M 
Millership, Steven J 
To, Wilson 

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.

Description

Keywords

Animals, Biological Variation, Population, DNA Methylation, Diet, High-Fat, Epigenesis, Genetic, Female, Genomic Imprinting, Mammals, Mice, Pregnancy

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Springer Science and Business Media LLC
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)