Lysine benzoylation is a histone mark regulated by SIRT2

Nat Commun. 2018 Aug 28;9(1):3374. doi: 10.1038/s41467-018-05567-w.


Metabolic regulation of histone marks is associated with diverse biological processes through dynamically modulating chromatin structure and functions. Here we report the identification and characterization of a histone mark, lysine benzoylation (Kbz). Our study identifies 22 Kbz sites on histones from HepG2 and RAW cells. This type of histone mark can be stimulated by sodium benzoate (SB), an FDA-approved drug and a widely used chemical food preservative, via generation of benzoyl CoA. By ChIP-seq and RNA-seq analysis, we demonstrate that histone Kbz marks are associated with gene expression and have physiological relevance distinct from histone acetylation. In addition, we demonstrate that SIRT2, a NAD+-dependent protein deacetylase, removes histone Kbz both in vitro and in vivo. This study therefore reveals a new type of histone marks with potential physiological relevance and identifies possible non-canonical functions of a widely used chemical food preservative.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / biosynthesis
  • Acyl Coenzyme A / chemistry
  • Animals
  • Drosophila melanogaster
  • Epigenesis, Genetic / drug effects
  • Food Preservatives / pharmacology*
  • Gene Expression Regulation / drug effects
  • Gene Knockout Techniques
  • HEK293 Cells
  • Hep G2 Cells
  • Histone Code / drug effects*
  • Histones / metabolism
  • Humans
  • Lysine / metabolism*
  • Mice
  • Promoter Regions, Genetic
  • RAW 264.7 Cells
  • Sirtuin 2 / genetics
  • Sirtuin 2 / metabolism*
  • Sodium Benzoate / pharmacology*


  • Acyl Coenzyme A
  • Food Preservatives
  • Histones
  • benzoyl-coenzyme A
  • SIRT2 protein, human
  • Sirt2 protein, mouse
  • Sirtuin 2
  • Lysine
  • Sodium Benzoate