Characterization of histone acylations links chromatin modifications with metabolism

Johayra Simithy, Simone Sidoli, Zuo-Fei Yuan, Mariel Coradin, Natarajan V. Bhanu, Dylan M. Marchione, Brianna J. Klein, Gleb A. Bazilevsky, Cheryl E. McCullough, Robert S. Magin, Tatiana G. Kutateladze, Nathaniel W. Snyder, Ronen Marmorstein and Benjamin A. Garcia ()
Additional contact information
Johayra Simithy: Perelman School of Medicine, University of Pennsylvania
Simone Sidoli: Perelman School of Medicine, University of Pennsylvania
Zuo-Fei Yuan: Perelman School of Medicine, University of Pennsylvania
Mariel Coradin: Perelman School of Medicine, University of Pennsylvania
Natarajan V. Bhanu: Perelman School of Medicine, University of Pennsylvania
Dylan M. Marchione: Perelman School of Medicine, University of Pennsylvania
Brianna J. Klein: University of Colorado School of Medicine
Gleb A. Bazilevsky: Perelman School of Medicine, University of Pennsylvania
Cheryl E. McCullough: University of Pennsylvania
Robert S. Magin: Perelman School of Medicine, University of Pennsylvania
Tatiana G. Kutateladze: University of Colorado School of Medicine
Nathaniel W. Snyder: Drexel University
Ronen Marmorstein: Abramson Family Cancer Research Institute, and the Department of Chemistry, University of Pennsylvania
Benjamin A. Garcia: Perelman School of Medicine, University of Pennsylvania

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Over the last decade, numerous histone acyl post-translational modifications (acyl-PTMs) have been discovered, of which the functional significance is still under intense study. Here, we use high-resolution mass spectrometry to accurately quantify eight acyl-PTMs in vivo and after in vitro enzymatic assays. We assess the ability of seven histone acetyltransferases (HATs) to catalyze acylations on histones in vitro using short-chain acyl-CoA donors, proving that they are less efficient towards larger acyl-CoAs. We also observe that acyl-CoAs can acylate histones through non-enzymatic mechanisms. Using integrated metabolomic and proteomic approaches, we achieve high correlation (R 2 > 0.99) between the abundance of acyl-CoAs and their corresponding acyl-PTMs. Moreover, we observe a dose-dependent increase in histone acyl-PTM abundances in response to acyl-CoA supplementation in in nucleo reactions. This study represents a comprehensive profiling of scarcely investigated low-abundance histone marks, revealing that concentrations of acyl-CoAs affect histone acyl-PTM abundances by both enzymatic and non-enzymatic mechanisms.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-01384-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01384-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-01384-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().