Metabolism and the Epigenome: A Dynamic Relationship

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...

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Bibliographic Details
Published in:Trends in biochemical sciences (Amsterdam. Regular ed.) 2020-09, Vol.45 (9), p.731-747
Main Authors: Haws, Spencer A., Leech, Cassandra M., Denu, John M.
Format: Article
Language:English
Subjects:
acetylation
acylation
chromatin
circadian cycles
dietary challenges
methylation
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Summary: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. Metabolites from diverse pathways act as essential cofactors for chromatin-modifying enzymes.Distinct reader domains of chromatin effectors facilitate the downstream functions for individual post-translational modifications.Metabolic enzymes are capable of acting as loci-specific regulators of the epigenome.Physiological fluctuations in metabolite cofactor availability can be stimulated by natural and exogenous stimuli.
ISSN:0968-0004
1362-4326
DOI:10.1016/j.tibs.2020.04.002