Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015:31:473-496.
doi: 10.1146/annurev-cellbio-100814-125544. Epub 2015 Sep 10.

Metabolism and epigenetics

Ryan Janke #  1 , Anne E Dodson #  1 , Jasper Rine  1
Affiliations
Review

Metabolism and epigenetics

Ryan Janke et al. Annu Rev Cell Dev Biol. 2015.

Abstract

Epigenetic mechanisms by which cells inherit information are, to a large extent, enabled by DNA methylation and posttranslational modifications of histone proteins. These modifications operate both to influence the structure of chromatin per se and to serve as recognition elements for proteins with motifs dedicated to binding particular modifications. Each of these modifications results from an enzyme that consumes one of several important metabolites during catalysis. Likewise, the removal of these marks often results in the consumption of a different metabolite. Therefore, these so-called epigenetic marks have the capacity to integrate the expression state of chromatin with the metabolic state of the cell. This review focuses on the central roles played by acetyl-CoA, S-adenosyl methionine, NAD(+), and a growing list of other acyl-CoA derivatives in epigenetic processes. We also review how metabolites that accumulate as a result of oncogenic mutations are thought to subvert the epigenetic program.

Keywords: S-adenosyl methionine; acetylation; chromatin modification; folate; methylation; oncometabolite.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The one-carbon pathway (brown arrows) is important for the production of methionine and cysteine, as well as the SAM used in DNA and histone methylation reactions. Several inputs into the pathway replenish metabolites consumed during one-carbon metabolism. In cells expressing threonine dehydrogenase, threonine is oxidized to produce glycine, which is converted to methylene-THF (blue arrows). Folate obtained through diet or by de novo synthesis is converted into THF. Abbreviations: Me, methyl; MTHFR, methylenetetrahydrofolate reductase; SAH, S-adenosyl homocysteine; SAM, S-adenosyl methionine; THF, tetrahydrofolate.
Figure 2
Figure 2
Potential roles of ascorbate and oncometabolites in regulating the activity of FeII- and α-ketoglutarate–dependent dioxygenases. (a) Following the oxidative decarboxylation of α-ketoglutarate, the dioxygenase can regain enzyme activity either by hydroxylating a substrate such as 5mC or by oxidizing ascorbate. (b) Mutations in IDH, SDH, and FH genes can result in high levels of oncometabolites (red) known to inhibit FeII- and α-ketoglutarate–dependent dioxygenases competitively with respect to α-ketoglutarate (green). Abbreviations: 5hmC, 5-hydroxymethylcytosine; 5mC, 5-methylcytosine; FH, fumarate hydratase; IDH, isocitrate dehydrogenase; SDH, succinate dehydrogenase.
Figure 3
Figure 3
Metabolic pathways used for synthesis of NAD+ in yeast and mammals. (a) The de novo NAD+ synthesis pathway converts tryptophan to quinolinate (blue box), which is then converted into NAMN, a precursor to NAD+. The NAD+ salvage pathway (light brown arrows) converts NAM, one of the by-products of sirtuin-mediated deacetylation, back into NAD+. Yeast converts NAM into NAD+ through the generation of NA. (b) Mammals are able to process NA in the same manner as yeast to generate NAD+. However, the mammalian salvage pathway does not generate NA; instead, NAM is converted into NMN and then directly back into NAD+. NAD+ is consumed during the deacetylation of histones catalyzed by sirtuins. Abbreviations: NA, nicotinic acid; NaAD, nicotinic acid adenine dinucleotide; NAD+, nicotinamide adenine dinucleotide; NAM, nicotinamide; NAMN, nicotinic acid mononucleotide; NAMPT, nicotinamide phosphoribosyltransferase; NMN, nicotinamide mononucleotide; OAAR, O-acetyl ADP-ribose.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Adam J, Yang M, Soga T, Pollard PJ. Rare insights into cancer biology. Oncogene. 2014;33(20):2547–56. - PubMed
    1. Allfrey VG, Faulkner R, Mirsky AE. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. PNAS. 1964;51(5):786–94. - PMC - PubMed
    1. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Cohen H, et al. Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels. J. Biol. Chem. 2002;277(21):18881–90. - PubMed
    1. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature. 2003;423(6936):181–85. - PMC - PubMed
    1. Apostolou E, Hochedlinger K. Chromatin dynamics during cellular reprogramming. Nature. 2013;502(7472):462–71. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources

  NODES
twitter 2