Metabolic regulation of gene expression through histone acylations

Nat Rev Mol Cell Biol. 2017 Feb;18(2):90-101. doi: 10.1038/nrm.2016.140. Epub 2016 Dec 7.


Eight types of short-chain Lys acylations have recently been identified on histones: propionylation, butyrylation, 2-hydroxyisobutyrylation, succinylation, malonylation, glutarylation, crotonylation and β-hydroxybutyrylation. Emerging evidence suggests that these histone modifications affect gene expression and are structurally and functionally different from the widely studied histone Lys acetylation. In this Review, we discuss the regulation of non-acetyl histone acylation by enzymatic and metabolic mechanisms, the acylation 'reader' proteins that mediate the effects of different acylations and their physiological functions, which include signal-dependent gene activation, spermatogenesis, tissue injury and metabolic stress. We propose a model to explain our present understanding of how differential histone acylation is regulated by the metabolism of the different acyl-CoA forms, which in turn modulates the regulation of gene expression.

Publication types

  • Review

MeSH terms

  • Acetyl Coenzyme A / metabolism
  • Acyl Coenzyme A / metabolism
  • Acylation
  • Animals
  • Fatty Acids, Volatile / metabolism
  • Gene Expression Regulation*
  • Histones / chemistry*
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism
  • Male
  • Protein Domains
  • Protein Processing, Post-Translational
  • Spermatogenesis
  • Stress, Physiological


  • Acyl Coenzyme A
  • Fatty Acids, Volatile
  • Histones
  • Acetyl Coenzyme A
  • Lysine