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. 2020 Jan 3;11:102. doi: 10.1038/s41467-019-13668-3

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — The activity of the TCA cycle is essential to provide the metabolites that control chromatin modifications and DNA methylation. Specifically, histone acetylation by histone acetyltransferases (HATs) is dependent on the availability of acetyl-CoA, which provides the necessary acetyl groups to enable the reaction. Acetyl-CoA is produced in the cytosol by ACLY using citrate exported from the TCA cycle in mitochondria. α-ketoglutarate (α-KG) is an essential cofactor of 2-OGDD, including the histone demethylases JMJDs and TET DNA demethylases. Succinate is the product of 2-OGDD enzymes reactions and thus, when it accumulates, it works as an antagonist of the reaction. 2-HG and fumarate can also rewire the epigenetic landscape of the cells through inhibition of histone and DNA demethylases.