Metabolism and the Epigenome: A Dynamic Relationship.

Spencer A Haws, Cassandra M Leech, John M Denu

Journal: Trends in biochemical sciences 2021;45(9):731-747

PMID: 32387193

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Abstract

Many chromatin-modifying enzymes require metabolic cofactors to support their catalytic activities, providing a direct path for fluctuations in metabolite availability to regulate the epigenome. Over the past decade, our knowledge of this link has grown significantly. What began with studies showing that cofactor availability drives global abundances of chromatin modifications has transitioned to discoveries highlighting metabolic enzymes as loci-specific regulators of gene expression. Here, we cover our current understanding of mechanisms that facilitate the dynamic and complex relationship between metabolism and the epigenome, focusing on the roles of essential metabolic and chromatin associated enzymes. We discuss physiological conditions where availability of these epimetabolites is dynamically altered, highlighting known links to the epigenome and proposing other plausible connections.

Address: Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53706, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA.; Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53706, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA. Electronic address: [email protected].

DOI: 10.1016/j.tibs.2020.04.002

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MeSH Terms: Acetylation, Chromatin, DNA Methylation, Epigenome