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The effect of prenatal under-nutrition on the expression of DNA methyltransferases and methyl CPG binding protein 2 in the liver after weaning

Lillycrop, K.A., Slater-Jefferies, J.L., Phillips, E.S., Jackson, A.A., Hanson, M.A. and Burdge, G.C. (2006) The effect of prenatal under-nutrition on the expression of DNA methyltransferases and methyl CPG binding protein 2 in the liver after weaning Early Human Development, 82, (8(A08)), pp. 495-496. (doi:10.1016/j.earlhumdev.2006.06.003).

Record type: Article

Abstract

Induction of an altered metabolic phenotype in the offspring of rats fed a protein-restricted (PR) diet during pregnancy involves hypomethylation and increased expression of the hepatic glucocorticoid receptor (GR) and PPARa promoters. To determine the mechanism responsible for promoter hypomethylation we investigated the effect of feeding a PR diet to pregnant rats on the expression of DNA methyltransferase (DMNT)-1 which maintains DNA methylation during mitosis, DNMT 3a and 3b which catalyse DNA methylation de novo, the DNA demethylase MBD2 and the methyl CpG binding protein (MeCP)-2 which recruits enzymes that regulate covalent histone modifications to methylated DNA in the liver of the adult offspring. Methods: Rats were fed either a control or PR diet from conception to delivery, and chow during lactation. Offspring were weaned onto chow at postnatal day 28 and killed at postnatal day 34. mRNA expression was determined by real-time quantitative RT PCR. Results: There was no effect of prenatal under-nutrition on the expression of DNMT 3a or 3b, or on the expression of MBD2. DNMT1 expression was significantly lower (17%, p b0.05) and MeCP2 expression was reduced (28.6%, p b0.05) in the PR offspring vs. controls. Discussion: These results suggest that prenatal undernutrition induces hypomethylation of the PPARa and GR promoters by reducing the capacity of DNMT1 to methylate hemimethylated DNA during mitosis. Thus induction of an altered phenotype by prenatal under-nutrition may be the result of impaired DNMT1 activity. Lower MeCP2 expression, together with hypomethylation of CpGs, may facilitate histone acetylation leading to increased transcription. Disclosure: Was this work supported by industry? No.

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Published date: August 2006
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 56405
URI: http://eprints.soton.ac.uk/id/eprint/56405
ISSN: 0378-3782
PURE UUID: 7219792c-b239-4cc7-aa56-25ce9f105737
ORCID for K.A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for E.S. Phillips: ORCID iD orcid.org/0000-0001-5268-4203
ORCID for G.C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967

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Date deposited: 08 Aug 2008
Last modified: 17 Jul 2017 14:30

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Contributors

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

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