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Genome-wide methylation and gene expression changes in newborn rats following maternal protein restriction and reversal by folic acid

Altobelli, Gioia; Bogdarina, Irina; Stupka, Elia; Clark, Adrian J.C.; Langley-Evans, Simon C.

Authors

Gioia Altobelli

Irina Bogdarina

Elia Stupka

Adrian J.C. Clark



Abstract

A large body of evidence from human and animal studies demonstrates that the maternal diet during pregnancy can programme physiological and metabolic functions in the developing fetus, effectively determining susceptibility to later disease. The mechanistic basis of such programming is unclear but may involve resetting of epigenetic marks and fetal gene expression. The aim of this study was to evaluate genome-wide DNA methylation and gene expression in the livers of newborn rats exposed to maternal protein restriction. On day one postnatally, there were 618 differentially expressed genes and 1183 differentially methylated regions (FDR 5%). The functional analysis of differentially expressed genes indicated a significant effect on DNA repair/cycle/maintenance functions and of lipid, amino acid metabolism and circadian functions. Enrichment for known biological functions was found to be associated with differentially methylated regions. Moreover, these epigenetically altered regions overlapped genetic loci associated with metabolic and cardiovascular diseases. Both expression changes and DNA methylation changes were largely reversed by supplementing the protein restricted diet with folic acid. Although the epigenetic and gene expression signatures appeared to underpin largely different biological processes, the gene expression profile of DNA methyl transferases was altered, providing a potential link between the two molecular signatures. The data showed that maternal protein restriction is associated with widespread differential gene expression and DNA methylation across the genome, and that folic acid is able to reset both molecular signatures.

Citation

Altobelli, G., Bogdarina, I., Stupka, E., Clark, A. J., & Langley-Evans, S. C. (2013). Genome-wide methylation and gene expression changes in newborn rats following maternal protein restriction and reversal by folic acid. PLoS ONE, 8, https://doi.org/10.1371/journal.pone.0082989

Journal Article Type Article
Acceptance Date Nov 8, 2013
Publication Date Dec 31, 2013
Deposit Date Mar 3, 2015
Publicly Available Date Mar 3, 2015
Journal PlosOne
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 8
Article Number e82989
DOI https://doi.org/10.1371/journal.pone.0082989
Public URL http://eprints.nottingham.ac.uk/id/eprint/28473
Publisher URL http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082989
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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