There is accumulating evidence that later life outcomes may be programmed in utero such that a malevolent foetal environment may predispose to a subsequent increased risk of obesity, type 2 diabetes and cardiovascular disease.
Insulin-like growth factor 2 is an imprinted gene (expressed only from the paternal allele), and an important mediator of fetal growth. The micro RNA, miR-483, is located between exons 4 and 5 of /Igf2/ and is co-expressed with /Igf2/. We are performing experiments to determine the function of miR-483 and to understand the separate roles of /Igf2/ and miR-483.
Epigenetic mechanisms including DNA methylation, histone modifications and non-coding RNAs offer dynamic, heritable and reversible mechanisms of modulating genome function and that may be able to respond to environmental cues such as nutritional status.
Deficiencies of micronutrients including folic acid, vitamin B6, vitamin B12, zinc and selenium have been shown to alter epigenetic marks including DNA and histone methylation. Therefore it is proposed that suboptimal nutrient supply during early embryonic development could program an alternative methylation pattern that preserves foetal viability at the expense of increased morbidity in adult life.In order to test this hypothesis we analysed methylation in the blood at a genome wide level and at specific loci and compared between children whose mothers diets were or were not supplemented with micronutrients.Funded by BBSRC.
Khulan B, Cooper WN, Skinner BM, Bauer J, Owens S, Prentice AM, Belteki G, Constancia M, Dunger D, Affara NA. Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia. Hum Mol Genet. 2012 Feb 20. [Epub ahead of print]
Cooper WN, Khulan B, Owens S, Elks CE, Seidel V, Prentice AM, Belteki G, Ong KK, Affara NA, Constância M, Dunger DB. DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial. FASEB J. 2012 Jan 20. [Epub ahead of print]
Cooper WN, Constância M. How genome-wide approaches can be used to unravel the remaining secrets of the imprintome. Brief Funct Genomics. 2010 Jul;9(4):315-28. Review.