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

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cam.issuedOnline2022-05-05
dc.contributor.authorVan De Pette, Mathew
dc.contributor.authorDimond, Andrew
dc.contributor.authorGalvão, António M
dc.contributor.authorMillership, Steven J
dc.contributor.authorTo, Wilson
dc.contributor.authorProdani, Chiara
dc.contributor.authorMcNamara, Gráinne
dc.contributor.authorBruno, Ludovica
dc.contributor.authorSardini, Alessandro
dc.contributor.authorWebster, Zoe
dc.contributor.authorMcGinty, James
dc.contributor.authorFrench, Paul MW
dc.contributor.authorUren, Anthony G
dc.contributor.authorCastillo-Fernandez, Juan
dc.contributor.authorWatkinson, William
dc.contributor.authorFerguson-Smith, Anne C
dc.contributor.authorMerkenschlager, Matthias
dc.contributor.authorJohn, Rosalind M
dc.contributor.authorKelsey, Gavin
dc.contributor.authorFisher, Amanda G
dc.contributor.orcidVan De Pette, Mathew [0000-0002-1423-5957]
dc.contributor.orcidDimond, Andrew [0000-0002-2996-2479]
dc.contributor.orcidUren, Anthony G [0000-0002-6019-7111]
dc.contributor.orcidCastillo-Fernandez, Juan [0000-0002-0034-8029]
dc.contributor.orcidFerguson-Smith, Anne C [0000-0002-7608-5894]
dc.contributor.orcidMerkenschlager, Matthias [0000-0003-2889-3288]
dc.contributor.orcidKelsey, Gavin [0000-0002-9762-5634]
dc.contributor.orcidFisher, Amanda G [0000-0003-3010-3644]
dc.date.accessioned2022-05-09T11:03:04Z
dc.date.available2022-05-09T11:03:04Z
dc.date.issued2022-05-05
dc.date.submitted2020-08-10
dc.date.updated2022-05-09T11:03:04Z
dc.description.abstractTransmission 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.
dc.identifier.doi10.17863/CAM.84298
dc.identifier.eissn2041-1723
dc.identifier.issn2041-1723
dc.identifier.others41467-022-30022-2
dc.identifier.other30022
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336879
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/136/2442
dc.subject/631/136/2434/1706
dc.subject/631/337/176/1988
dc.subject/631/337/176/1968
dc.subject/631/1647/245/2222
dc.subject/59/5
dc.subject/45/91
dc.subject/64/60
dc.subject/49/23
dc.subject/14/19
dc.subject/45/88
dc.subject/13/51
dc.subjectarticle
dc.titleEpigenetic changes induced by in utero dietary challenge result in phenotypic variability in successive generations of mice.
dc.typeArticle
dcterms.dateAccepted2022-04-13
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
pubs.funder-project-idWellcome Trust (Wellcome) (ISSF PS3125_WCMA, 099276/Z/12/Z)
pubs.funder-project-idRCUK | Medical Research Council (MRC) (MC_U120027516, MC_UP_1605/11, MR/S000437/1, MC_U120027516, MC_UP_1605/12)
pubs.funder-project-idRCUK | Biotechnology and Biological Sciences Research Council (BBSRC) (BB/P002307/1, BB/P008623/1, BBS/E/B/000C0423)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-022-30022-2

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