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Review
. 2018 Apr 1;98(2):667-695.
doi: 10.1152/physrev.00010.2017.

Dietary Modulation of the Epigenome

Folami Y Ideraabdullah  1 , Steven H Zeisel  1
Affiliations
Review

Dietary Modulation of the Epigenome

Folami Y Ideraabdullah et al. Physiol Rev. .

Abstract

Epigenetics is the study of heritable mechanisms that can modify gene activity and phenotype without modifying the genetic code. The basis for the concept of epigenetics originated more than 2,000 yr ago as a theory to explain organismal development. However, the definition of epigenetics continues to evolve as we identify more of the components that make up the epigenome and dissect the complex manner by which they regulate and are regulated by cellular functions. A substantial and growing body of research shows that nutrition plays a significant role in regulating the epigenome. Here, we critically assess this diverse body of evidence elucidating the role of nutrition in modulating the epigenome and summarize the impact such changes have on molecular and physiological outcomes with regards to human health.

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Figures

FIGURE 1.
FIGURE 1.
Epigenetic regulation of the genome. Components required and pathway of events leading to epigenetic regulation of the genome. Arrows below show components of this pathway that are altered by diet. Arrows above indicate potential for epigenetic changes to be a response to genomic or physiological outcomes rather than a causal factor.
FIGURE 2.
FIGURE 2.
Epigenetic markers and targets. Three categories of epigenetic markers, their primary targets, and most common marks found in mammals. Closed circles represent methylated CpGs, shaded circles represent hydroxmethylated CpGs, and open circles represent unmodified CpGs.
FIGURE 3.
FIGURE 3.
Proposed model of timing of epimutation event and stability over lifespan. Model shows how the timing of environmentally induced epimutations may differentially affect epigenetic state across the lifespan. A: human developmental stages across lifespan. B: unperturbed DNA methylation levels at different stages of human development depicted in A. Methylation levels are shown increasing on the y-axis; each horizontal blue line indicates unperturbed methylation levels for different cell lineages in body, and waves in line indicate naturally occurring minor fluctuations in methylation levels over time. C–E: epimutation initiated during different stages of development (red “X” indicates timing of event) and mitotic inheritance/stability over the developmental timeline (red line indicates perturbed epigenetic state). C: epimutation initiated in germ cells but reset during somatic cell epigenetic reprogramming. D: epimutation initiated in germ cells or zygote and not reset during somatic cell epigenetic reprogramming affects multiple cell lineages and may persist throughout lifespan. E: epimutation initiated after somatic cell lineage determination/epigenetic reprogramming is usually cell lineage specific.
FIGURE 4.
FIGURE 4.
Nutrients as donors of epigenetic marks. Components of the one carbon metabolism pathway and TCA cycle that directly contribute the epigenetic marks for DNA and histone modifications. C, cytosine; G, guanine; CH3, methyl group; CH2OH, hydroxylmethyl group; Ac, acetyl group; Su, succinyl group; Ma, malonyl group; Glu, glutaryl group; TETs, ten-eleven-translocation enzymes; DNMTs, DNA methyltransferase enzymes; HMTs, histone methyltransferase enzymes; HATs, histone acetyltransferase enzymes; K, lysine; R, arginine; 5-MTHF, 5-methyltetrahydrofolate; SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine.
FIGURE 5.
FIGURE 5.
Nutrients as regulators of enzymatic activity. Nutrients and nutrient metabolites that alter activity of epigenetic regulatory enzymes. Solid arrows indicate increased enzymatic activity in the presence of the nutrient shown, and lines with blunted ends represent decreased/inhibited activity in the presence of nutrient shown. C, cytosine; G, guanine; CH3, methyl group; CH2OH, hydroxymethyl group; Ac, acetyl group; Fe2+, iron; VitC, vitamin C; FAD, flavin adenine dinucleotide; TETs, ten-eleven-translocation enzymes; DNMTs, DNA methyltransferase enzymes; HMTs, histone methyltransferase enzymes; HATs, histone acetyltransferase enzymes.
FIGURE 6.
FIGURE 6.
Epigenetic markers as mediators of nutrient signaling. Example of pathways of mediation of nutrient signaling via noncoding RNA molecules.
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