Diverse Activities of Histone Acylations Connect Metabolism to Chromatin Function - PubMed (original) (raw)

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Diverse Activities of Histone Acylations Connect Metabolism to Chromatin Function

Arnob Dutta et al. Mol Cell. 2016.

Abstract

Modifications of histones play important roles in balancing transcriptional output. The discovery of acyl marks, besides histone acetylation, has added to the functional diversity of histone modifications. Since all modifications use metabolic intermediates as substrates for chromatin-modifying enzymes, the prevalent landscape of histone modifications in any cell type is a snapshot of its metabolic status. Here, we review some of the current findings of how differential use of histone acylations regulates gene expression as response to metabolic changes and differentiation programs.

Keywords: YEATS domain; bromodomain; histone acylation; metabolism.

Copyright © 2016 Elsevier Inc. All rights reserved.

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Figure 1

Figure 1

The levels and types of short chain histone lysine acylations are influenced by metabolism. The levels of short chain acyl metabolic intermediates increase or decrease (arrows) dependent on metabolic state. These include acetate, crotonate, butyrate, β-hydroxybutyrate, and more. When conjugated to coenzyme A (CoA) these short acyl-CoAs function in fatty acid metabolism and can be used by acyl-transferases to modify lysines on histones within nucleosomes (disks). The levels of each type of histone acylation (e.g. acetylation Ac, crotonylation Cr, butyrylation Bu and β-hydroxybutyrylation Bhb) are influenced by the levels of these metabolites in the cell. Thus, metabolism affects the type and levels of histone acylation in chromatin and chromatin can in principle serve as a reservoir of these metabolites. Recent work suggests this will have epigenetic effects on chromatin function. Bromodomain-containing chromatin modifying complexes interact (arrow) with nucleosomes containing acetylated histones (Ac). By contrast, histone butyrylation (Bu), and perhaps other acylations, reduce or resist (blocked line) bromodomain containing protein complex interaction with nucleosomes. Histone acetylation and histone butyrylation are in competition (double arrow) with each other leading to dynamic interactions of bromodomain-containing complexes with nucleosomes. Acylations other than acetylation may have reader domain proteins that prefer those modifications. For example YEATS domain containing chromatin modifying complexes prefer to interact (arrow) with nucleosomes containing crotonylated (Cr) histones.

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References

    1. Alexander PB, Wang J, McKnight SL. Targeted killing of a mammalian cell based upon its specialized metabolic state. Proceedings of the National Academy of Sciences of the United States of America. 2011;108:15828–15833. - PMC - PubMed
    1. Allfrey VG, Faulkner R, Mirsky AE. Acetylation and Methylation of Histones and Their Possible Role in the Regulation of Rna Synthesis. Proceedings of the National Academy of Sciences of the United States of America. 1964;51:786–794. - PMC - PubMed
    1. Andrews FH, Shinsky SA, Shanle EK, Bridgers JB, Gest A, Tsun IK, Krajewski K, Shi X, Strahl BD, Kutateladze TG. The Taf14 YEATS domain is a reader of histone crotonylation. Nature chemical biology. 2016;12:396–398. - PMC - PubMed
    1. Anne-Lise Steunou DR, Jacques Côté. Regulating Chromatin by Histone Acetylation. Fundamentals of Chromatin. 2013:147–212.
    1. Aparicio OM, Billington BL, Gottschling DE. Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae. Cell. 1991;66:1279–1287. - PubMed

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