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).

Download

Full text not available from this repository.

Description/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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1016/j.earlhumdev.2006.06.003
ISSNs: 0378-3782 (print)
Subjects:
ePrint ID: 56405
Date :
Date Event
August 2006Published
Date Deposited: 08 Aug 2008
Last Modified: 16 Apr 2017 17:41
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/56405

Actions (login required)

View Item View Item