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
. 2016 Sep:22:349-360.
doi: 10.2119/molmed.2016.00051. Epub 2016 Apr 18.

Compartmentation of metabolites in regulating epigenome of cancer

Zhiqiang Zhao  1 , Li Wang  1   2 , Lijun Di  1
Affiliations

Compartmentation of metabolites in regulating epigenome of cancer

Zhiqiang Zhao et al. Mol Med. 2016 Sep.

Abstract

Covalent modification of DNA and histones are important epigenetic events and the genome wide reshaping of epigenetic markers is common in cancer. The epigenetic markers are produced by enzymatic reactions and some of these reactions require the presence of metabolites as cofactors (termed Epigenetic Enzyme Required Metabolites, EERMs). Recent studies found that the abundance of these EERMs correlates with epigenetic enzyme activities. Also, the subcellular compartmentation, especially the nuclear localization of these EERMs may play a role in regulating the activities of epigenetic enzymes. Moreover, gene specific recruitment of enzymes which produce the EERMs in the proximity of the epigenetic modification events accompanying the gene expression regulation, were proposed. Therefore, it is of importance to summarize these findings of the EERMs in regulating the epigenetic modifications at both DNA and histone levels, and to understand how EERMs contribute to cancer development by addressing their global versus local distribution.

Keywords: DNA methylation; EERM; Epigenetics; cancer cell metabolism; gene regulation; histone modification; metabolites.

PubMed Disclaimer

Conflict of interest statement

DISCLOSURE

The authors declare that they have no competing interests as defined by Molecular Medicine, or other interests that might be perceived to influence the results and discussion reported in this paper.

Figures

Figure 1.
Figure 1.
Epigenetic markers and EERMs. Schematic representation of epigenetic markers on histone tails and DNA strand. Various enzymes (E) are responsible for the generation of epigenetic modification including DNA methylation/demethylation, histone acetylation/deacetylation, histone methylation/demethylation, histone biotinylation, crotonylation, phosphorylation and glycosylation with the presence of EERMs (dark green) including SAM, α-KG, FAD, acetyl-CoA, NAD+, crotonyl-CoA and O-GlcNAc
Figure 2.
Figure 2.
Global impact of EERMs on nuclear epigenetic events. The EERMs (dark green) including NAD+, NADH, SAM, Acetyl-CoA and α-KG are mainly synthesized within cytoplasm and their cytoplasmic concentration is regulated through multiple metabolic pathways. These EERMs are freely permeabilized into the nucleus and act as cofactors for epigenetic modification enzymes. The metabolism precursors and co-enzymes (light green) that are necessary for synthesizing EERMs are absorbed mainly from extracellular supplies and their abundance may modulate the nuclear epigenetic activities via EERMs indirectly.
Figure 3.
Figure 3.
Local enrichment of EERMs and epigenetic modification. EERMs (green balls) can be produced in both the cytoplasm and nucleus, depending on the distribution of the EERM-producing enzymes. The EERM-producing enzymes localized in the nucleus may increase the enrichment of EERMs locally, facilitating the global regulation of epigenetic modifications by the EERM-dependent epigenetic modifiers. The EERM-producing enzymes may also form complexes with EERM-dependent epigenetic modifiers and/or gene-specific transcription factors and provide a local supply of EERMs to gene-specific regulation of epigenetic modifications.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Henikoff S, Matzke MA. Exploring and explaining epigenetic effects. Trends Genet. 1997;13:293–5. - PubMed
    1. Herceg Z, Vaissiere T. Epigenetic mechanisms and cancer: an interface between the environment and the genome. Epigenetics. 2011;6:804–19. - PubMed
    1. Rossetto D, Avvakumov N, Cote J. Histone phosphorylation: a chromatin modification involved in diverse nuclear events. Epigenetics. 2012;7:1098–108. - PMC - PubMed
    1. Shiio Y, Eisenman RN. Histone sumoylation is associated with transcriptional repression; Proc Natl Acad Sci U S A; 2003. pp. 13225–30. - PMC - PubMed
    1. Tan M, et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 2011;146:1016–28. - PMC - PubMed

LinkOut - more resources