Chromatin as a key consumer in the metabolite economy.

TitleChromatin as a key consumer in the metabolite economy.
Publication TypeJournal Article
Year of Publication2020
AuthorsDiehl, KL, Muir, TW
JournalNat Chem Biol
Volume16
Issue6
Pagination620-629
Date Published2020 06
ISSN1552-4469
KeywordsChromatin, Chromatin Assembly and Disassembly, DNA Damage, DNA Repair, Enzymes, Epigenesis, Genetic, Eukaryota, Histones, Humans, Metabolic Networks and Pathways, Protein Processing, Post-Translational
Abstract

<p>In eukaryotes, chromatin remodeling and post-translational modifications (PTMs) shape the local chromatin landscape to establish permissive and repressive regions within the genome, orchestrating transcription, replication, and DNA repair in concert with other epigenetic mechanisms. Though cellular nutrient signaling encompasses a huge number of pathways, recent attention has turned to the hypothesis that the metabolic state of the cell is communicated to the genome through the type and concentration of metabolites in the nucleus that are cofactors for chromatin-modifying enzymes. Importantly, both epigenetic and metabolic dysregulation are hallmarks of a range of diseases, and this metabolism-chromatin axis may yield a well of new therapeutic targets. In this Perspective, we highlight emerging themes in the inter-regulation of the genome and metabolism via chromatin, including nonenzymatic histone modifications arising from chemically reactive metabolites, the expansion of PTM diversity from cofactor-promiscuous chromatin-modifying enzymes, and evidence for the existence and importance of subnucleocytoplasmic metabolite pools.</p>

DOI10.1038/s41589-020-0517-x
Alternate JournalNat Chem Biol
PubMed ID32444835
PubMed Central IDPMC7258299
Grant ListP01 CA196539 / CA / NCI NIH HHS / United States
R37 GM086868 / GM / NIGMS NIH HHS / United States
R01 GM107047 / GM / NIGMS NIH HHS / United States
F32 CA206418 / CA / NCI NIH HHS / United States