Epigenetic mechanisms for nutrition determinants of later health outcomes

Abstract

Epigenetic marking on genes can determine whether or not genes are expressed. Epigenetic regulation is mediated by the addition of methyl groups to DNA cytosine bases, of methyl and acetyl groups to proteins (histones) around which DNA is wrapped, and by small interfering RNA molecules. Some components of epigenetic regulation have evolved to permit control of whether maternal or paternal genes are expressed. The epigenetic imprinting of IGF2 expression is an example of maternal and paternal epigenetic marking that modulates fetal growth and fetal size. However, epigenetic regulation also permits the fetus and the infant to adapt gene expression to the environment in which it is growing; sometimes when this adjustment goes awry, the risk of chronic disease is increased. Recent progress in the understanding of nutritional influences on epigenetics suggests that nutrients that are part of methyl-group metabolism can significantly influence epigenetics. During critical periods in development, dietary methyl-group intake (choline, methionine, and folate) can alter DNA and histone methylation, which results in lifelong changes in gene expression. In rodent models, pregnant dams that were fed diets high in methionine, folic acid, and choline produced offspring with different coat colors or with kinked tails. A number of syndromes in humans can be caused by defective epigenetic regulation, including Rett syndrome. There are interesting examples of the effects of nutrition in early life that result in altered health in adults, and some of these could be the result of altered epigenetic regulation of gene expression.

FIGURE 1

Epigenetic marks alter gene expression. Normally, transcription factors bind to promoter regions of DNA and induce gene expression producing mRNA. However, when specific CpG islands in the promoter are methylated, capping proteins that prevent access of the transcription factor to DNA are attracted, and gene expression is suppressed. mRNA, messenger RNA; TF, transcription factor.

FIGURE 2

Choline-methionine-folate interactions. These 3 nutrients are metabolically interrelated. Methyl-THF, 5-methyl tetrahydrofolate; SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine; PEMT, phosphatidylethanolamine-N-methyltransferase.