Investigation of the role of epigenetic modification of the rat glucokinase gene in fetal programming

Irina Bogdarina, Helena C. Murphy, Shamus P. Burns, Adrian J.L. Clark

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Fetal malnutrition is associated with development of impaired glucose tolerance, diabetes and hypertension in later life in humans and several mammalian species. The mechanisms that underlie this phenomenon of fetal programming are unknown. We hypothesize that adverse effects in utero and early life may influence the basal expression levels of certain genes such that they are re-set with long-term consequences for the organism. An excellent candidate mechanism for this re-setting process is DNA methylation, since post-natal methylation patterns are largely established in utero. We have sought to test this hypothesis by investigating the glucokinase gene (Gck) in rat offspring programmed using a maternal low protein diet model (MLP). Northern blot reveals that fasting levels of Gck expression are reduced after programming, although this distinction disappears after feeding. Bisulphite sequencing of the hepatic Gck promoter indicates a complete absence of methylation at the 12 CpG sites studied in controls and MLP animals. Non-expressing cardiac tissue also showed no DNA methylation in this region, whereas brain and all fetal tissues were fully methylated. These findings are not consistent with the hypothesis that programming results from differential methylation of Gck. However, it remains possible that programming may influence methylation patterns in Gck at a distance from the promoter, or in genes encoding factors that regulate basal Gck expression.
Original languageEnglish
Pages (from-to)1407-1415
Number of pages9
JournalLife Sciences
Volume74
Issue number11
Early online date29 Nov 2003
DOIs
Publication statusPublished - 30 Jan 2004
Externally publishedYes

Fingerprint

Glucokinase
Fetal Development
Epigenomics
Rats
Methylation
Genes
DNA Methylation
Gene expression
Fetal Nutrition Disorders
Tissue
Gene Expression
Protein-Restricted Diet
Gene encoding
Glucose Intolerance
Nutrition
Medical problems
Northern Blotting
Fasting
Brain
Animals

Cite this

Bogdarina, Irina ; Murphy, Helena C. ; Burns, Shamus P. ; Clark, Adrian J.L. / Investigation of the role of epigenetic modification of the rat glucokinase gene in fetal programming. In: Life Sciences. 2004 ; Vol. 74, No. 11. pp. 1407-1415.
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Investigation of the role of epigenetic modification of the rat glucokinase gene in fetal programming. / Bogdarina, Irina; Murphy, Helena C.; Burns, Shamus P.; Clark, Adrian J.L.

In: Life Sciences, Vol. 74, No. 11, 30.01.2004, p. 1407-1415.

Research output: Contribution to journalArticle

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