Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 19 (12)

Metabolic Signaling Into Chromatin Modifications in the Regulation of Gene Expression

Affiliations
Review

Metabolic Signaling Into Chromatin Modifications in the Regulation of Gene Expression

Tian Gao et al. Int J Mol Sci.

Abstract

The regulation of cellular metabolism is coordinated through a tissue cross-talk by hormonal control. This leads to the establishment of specific transcriptional gene programs which adapt to environmental stimuli. On the other hand, recent advances suggest that metabolic pathways could directly signal into chromatin modifications and impact on specific gene programs. The key metabolites acetyl-CoA or S-adenosyl-methionine (SAM) are examples of important metabolic hubs which play in addition a role in chromatin acetylation and methylation. In this review, we will discuss how intermediary metabolism impacts on transcription regulation and the epigenome with a particular focus in metabolic disorders.

Keywords: chromatin; epigenetics; metabolic signaling; obesity.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Interaction between metabolism and histone acetylation and DNA/histone methylation. Different nutrient substrates including glucose, fatty acids, amino acids and acetate lead to production of intermediary metabolites which play a role in protein acetylation. Acetyl-CoA derived from glucose, fatty acid or amino acid metabolism is the substrate for histone acetylation after conversion into citrate by TCA cycle and back to Acetyl-CoA in the cytoplasm by ACLY. Acetate is also a source of acetyl-CoA which leads to histone acetylation. Histone and DNA methylation depends on the dietary methionine which enters a cycle for conversion into SAM which is used as a donor of the methyl group. This leads to formation of SAH which is recycled back to methionine through methylation of homocysteine. PDC: Pyruvate Dehydrogenase Complex; ACLY: ATP-dependent Citrate Lyase; SAM: S-Adenosylmethionine; SAH: S-Adenosyl-Homocysteine; DNMTs, DNA N-Methyltransferase; MATs: Methionine Adenosyltransferase. Dashed arrows: multiple-step metabolic pathway; solid arrows: one-step metabolic reaction.
Figure 2
Figure 2
Influence of different diets in chromatin function. Ketogenic diet promotes increased fatty acid oxidation rates which elevates acetyl-CoA production and therefore ketone bodies. The ketone body β-hydroxybutyrate inhibits class I HDACs leading to increased H3K9ac and H3K14ac. Calorie restriction leads to increased NAD+ levels and activation of SIRT1 and SIRT6, which promote histone deacetylation and delays aging. Nutrient overload leads to obesity, it is not fully understood how acetyl-CoA pools may affect specific gene programs in the context of obesity. HDACS: Histone Deacetylases; HATS: Histone Acetyltransferases.

Similar articles

See all similar articles

Cited by 3 articles

References

    1. Jacob F., Monod J. Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol. 1961;3:318–356. doi: 10.1016/S0022-2836(61)80072-7. - DOI - PubMed
    1. Allfrey V.G., Faulkner R., Mirsky A.E. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc. Natl. Acad. Sci. USA. 1964;51:786–794. doi: 10.1073/pnas.51.5.786. - DOI - PMC - PubMed
    1. Pietrocola F., Galluzzi L., Manuel J., Pedro B.-S., Madeo F., Kroemer G. Cell Metabolism Review Acetyl Coenzyme A: A Central Metabolite and Second Messenger. Cell Metab. 2015;21:805–821. doi: 10.1016/j.cmet.2015.05.014. - DOI - PubMed
    1. Shi L., Tu B.P. Acetyl-CoA and the regulation of metabolism: Mechanisms and consequences. Curr. Opin. Cell Biol. 2015;33:125–131. doi: 10.1016/j.ceb.2015.02.003. - DOI - PMC - PubMed
    1. Cai L., Sutter B.M., Li B., Tu B.P. Acetyl-CoA Induces Cell Growth and Proliferation by Promoting the Acetylation of Histones at Growth Genes. Mol. Cell. 2011;42:426–437. doi: 10.1016/j.molcel.2011.05.004. - DOI - PMC - PubMed
Feedback