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, Benjamin A. Garcia

Research output: Contribution to journalArticle

47 Scopus citations

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.

Original languageEnglish (US)
Article number1141
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Simithy, J., Sidoli, S., Yuan, Z. F., Coradin, M., Bhanu, N. V., Marchione, D. M., Klein, B. J., Bazilevsky, G. A., McCullough, C. E., Magin, R. S., Kutateladze, T. G., Snyder, N. W., Marmorstein, R., & Garcia, B. A. (2017). Characterization of histone acylations links chromatin modifications with metabolism. Nature communications, 8(1), [1141]. https://doi.org/10.1038/s41467-017-01384-9