Chromatin As a Key Consumer in the Metabolite Economy

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2020 May 24

PMID 32444835

Citations 35

Authors

Katharine L Diehl

Tom W Muir

Affiliations

Soon will be listed here.

Abstract

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.

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References

Kornberg R . Structure of chromatin. Annu Rev Biochem. 1977; 46:931-54. DOI: 10.1146/annurev.bi.46.070177.004435. View

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

Jenuwein T, Allis C . Translating the histone code. Science. 2001; 293(5532):1074-80. DOI: 10.1126/science.1063127. View

Zoghbi H, Beaudet A . Epigenetics and Human Disease. Cold Spring Harb Perspect Biol. 2016; 8(2):a019497. PMC: 4743078. DOI: 10.1101/cshperspect.a019497. View

Chi P, Allis C, Wang G . Covalent histone modifications--miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer. 2010; 10(7):457-69. PMC: 3262678. DOI: 10.1038/nrc2876. View

Cai L, Sutter B, Li B, Tu B . Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Mol Cell. 2011; 42(4):426-37. PMC: 3109073. DOI: 10.1016/j.molcel.2011.05.004. View

Shyh-Chang N, Locasale J, Lyssiotis C, Zheng Y, Teo R, Ratanasirintrawoot S . Influence of threonine metabolism on S-adenosylmethionine and histone methylation. Science. 2012; 339(6116):222-6. PMC: 3652341. DOI: 10.1126/science.1226603. View

Ryu K, Nandu T, Kim J, Challa S, DeBerardinis R, Kraus W . Metabolic regulation of transcription through compartmentalized NAD biosynthesis. Science. 2018; 360(6389). PMC: 6465534. DOI: 10.1126/science.aan5780. View

Li S, Swanson S, Gogol M, Florens L, Washburn M, Workman J . Serine and SAM Responsive Complex SESAME Regulates Histone Modification Crosstalk by Sensing Cellular Metabolism. Mol Cell. 2015; 60(3):408-21. DOI: 10.1016/j.molcel.2015.09.024. View

10.

Wellen K, Hatzivassiliou G, Sachdeva U, Bui T, Cross J, Thompson C . ATP-citrate lyase links cellular metabolism to histone acetylation. Science. 2009; 324(5930):1076-80. PMC: 2746744. DOI: 10.1126/science.1164097. View

11.

Yang M, Soga T, Pollard P . Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013; 123(9):3652-8. PMC: 3754247. DOI: 10.1172/JCI67228. View

12.

Ye C, Sutter B, Wang Y, Kuang Z, Tu B . A Metabolic Function for Phospholipid and Histone Methylation. Mol Cell. 2017; 66(2):180-193.e8. PMC: 5482412. DOI: 10.1016/j.molcel.2017.02.026. View

13.

Bulusu V, Tumanov S, Michalopoulou E, van den Broek N, Mackay G, Nixon C . Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. Cell Rep. 2017; 18(3):647-658. PMC: 5276806. DOI: 10.1016/j.celrep.2016.12.055. View

14.

Schvartzman J, Thompson C, Finley L . Metabolic regulation of chromatin modifications and gene expression. J Cell Biol. 2018; 217(7):2247-2259. PMC: 6028552. DOI: 10.1083/jcb.201803061. View

15.

Suganuma T, Workman J . Chromatin and Metabolism. Annu Rev Biochem. 2018; 87:27-49. DOI: 10.1146/annurev-biochem-062917-012634. View

16.

Li X, Egervari G, Wang Y, Berger S, Lu Z . Regulation of chromatin and gene expression by metabolic enzymes and metabolites. Nat Rev Mol Cell Biol. 2018; 19(9):563-578. PMC: 6907087. DOI: 10.1038/s41580-018-0029-7. View

17.

Galligan J, Marnett L . Histone Adduction and Its Functional Impact on Epigenetics. Chem Res Toxicol. 2016; 30(1):376-387. PMC: 5257195. DOI: 10.1021/acs.chemrestox.6b00379. View

18.

Kulkarni R, Worth A, Zengeya T, Shrimp J, Garlick J, Roberts A . Discovering Targets of Non-enzymatic Acylation by Thioester Reactivity Profiling. Cell Chem Biol. 2017; 24(2):231-242. PMC: 5864104. DOI: 10.1016/j.chembiol.2017.01.002. View

19.

Simithy J, Sidoli S, Yuan Z, Coradin M, Bhanu N, Marchione D . Characterization of histone acylations links chromatin modifications with metabolism. Nat Commun. 2017; 8(1):1141. PMC: 5656686. DOI: 10.1038/s41467-017-01384-9. View

20.

Galligan J, L Rose K, Beavers W, Hill S, Tallman K, Tansey W . Stable histone adduction by 4-oxo-2-nonenal: a potential link between oxidative stress and epigenetics. J Am Chem Soc. 2014; 136(34):11864-6. PMC: 4151707. DOI: 10.1021/ja503604t. View