Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation

Abstract

DNA methylation is the most extensively studied mechanism of epigenetic gene regulation. Increasing evidence indicates DNA methylation is labile in response to nutritional and environmental influences. Alternations in DNA methylation profiles can lead to changes in gene expression, resulting in diverse phenotypes with the potential for increased disease risk. The primary methyl donor for DNA methylation is S-adenosylmethionine (SAM), a species generated in the cyclical cellular process called one-carbon metabolism. One-carbon metabolism is catalyzed by several enzymes in the presence of dietary micronutrients, including folate, choline, betaine, and other B vitamins. For this reason, nutrition status, particularly micronutrient intake, has been a focal point when investigating epigenetic mechanisms. Though animal evidence linking nutrition and DNA methylation is fairly extensive, epidemiological evidence is less comprehensive. This review serves to integrate studies of the animal in vivo with human epidemiological data pertaining to nutritional regulation of DNA methylation, and to further identify areas in which current knowledge is limited.

Meat nutritional composition and nutritive role in the human diet

“…Together with B12, folic acid is an important methyl donor which is crucial for fetal development (Zeisel, 2009) and it seems to be important in DNA methylation, being associated with cancer prevention (Anderson, Sant, & Dolinoy, 2012). Liver, especially from pigs, is a great source of folic acid supplying 81% of DR while calf liver supplies 87% of DR.…”

Foetal Programming and Consequences

“…An exciting discovery was the demonstration that nutrients influence gene function by interacting with nuclear receptors (vitamins A and D) and also through epigenetic mechanisms (folate, vitamin B 12 , etc.) (Anderson et al, 2012). Both mechanisms modulate gene expression.…”

The effects of methyl-donor deficiency on mutation induction and transgenerational instability in mice

“…The 5-methylTHF is used in the one-carbon metabolism cycle by donating its methyl group to homocysteine, converting it to methionine (Eto et al, 1986;Beetstra et al, 2005) and by that, replenishing cellular SAM (Caudill et al, 2001;Fenech, 2001;Anderson et al, 2012). This favours the increase in the dUMP pool and promotes an even bigger uracil incorporation into DNA.…”

“…Many current studies use a candidate gene-specific approach to examine the effects of folate on DNA methylation. The selected genomic loci are usually linked with a disease outcome of interest (in preventative or therapeutic strategies) such as cancer or diabetes, and these studies usually explore folate's role in methylation of target tissue types (Anderson et al, 2012). Similarly, a cohort study in Netherlands showed that low-folate intake combined with high alcohol consumption resulted in non-significant changes in gene promoter methylation in blood of CRC patients (Van Engeland et al, 2003).…”

“…The data combined suggest that folate plays an important role in DNA methylation and even though the link is still unclear, folate could be associated with protection against some cancers. (Kim, 2003;Kim, 2004;Anderson et al, 2012).…”