The University of Southampton
University of Southampton Institutional Repository

Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications

Record type: Article

Prenatal nutritional constraint induces an altered metabolic phenotype in the offspring which in humans confers an increased risk of non-communicable disease. Feeding a protein-restricted (PR) diet to pregnant rats causes hypomethylation of specific gene promoters in the offspring and alters the phenotype. We investigated how altered epigenetic regulation of the hepatic glucocorticoid receptor (GR) 110 promoter is induced in the offspring. Rats were fed a control (180 g casein/kg) or a PR (90 g casein/kg) diet throughout pregnancy, and chow during lactation. Offspring were killed at postnatal day 34 (n 5 per maternal dietary group). Methylation-sensitive PCR showed that GR110 promoter methylation was 33 % lower (P < 0·001) and GR expression 84 % higher (P < 0·05) in the PR offspring. Reverse transcription–PCR showed that DNA methyltransferase-1 (Dnmt1) expression was 17 % lower (P < 0·05) in PR offspring, while Dnmt3a/b and methyl binding domain protein-2 expression was not altered. Thus hypomethylation of the GR110 promoter may result from lower capacity to methylate hemimethylated DNA during mitosis. Histone modifications which facilitate transcription were increased at the GR110 promoter (147–921 %, P < 0·001), while those that suppress methylation were decreased (54 %, P < 0·01) or similar to controls. In human umbilical cord (n 15), there was a 2-fold difference between the highest and lowest level of GR1-CTotal promoter methylation. Dnmt1, but not Dnmt3a, expression predicted 49 % (P = 0·003) of the variation in GR1-CTotal promoter methylation. These findings suggest that induction in the offspring of altered epigenetic regulation of the hepatic GR110 promoter, and hence metabolic phenotype, may be due to reduced Dnmt1 expression.

Full text not available from this repository.

Citation

Lillycrop, K.A., Slater-Jefferies, J.L., Hanson, M.A., Godfrey, K.M., Jackson, A.A. and Burdge, G.C. (2007) Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications British Journal of Nutrition, 97, (6), pp. 1064-1073. (doi:10.1017/S000711450769196X).

More information

Published date: 1 June 2007
Keywords: fetal programming, epigenetic, rat, glucocorticoid receptor, histones, human

Identifiers

Local EPrints ID: 56263
URI: http://eprints.soton.ac.uk/id/eprint/56263
ISSN: 0007-1145
PURE UUID: 35c66440-a76a-43e8-b2f9-e680c34f2baf
ORCID for K.A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for K.M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for G.C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967

Catalogue record

Date deposited: 08 Aug 2008
Last modified: 17 Jul 2017 14:31

Export record

Altmetrics

Contributors

Author: K.A. Lillycrop ORCID iD
Author: J.L. Slater-Jefferies
Author: M.A. Hanson
Author: K.M. Godfrey ORCID iD
Author: A.A. Jackson
Author: G.C. Burdge ORCID iD

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×