Class I histone deacetylases are major histone decrotonylases: evidence for critical and broad function of histone crotonylation in transcription

Cell Res. 2017 Jul;27(7):898-915. doi: 10.1038/cr.2017.68. Epub 2017 May 12.


Recent studies on enzymes and reader proteins for histone crotonylation support a function of histone crotonylation in transcription. However, the enzyme(s) responsible for histone decrotonylation (HDCR) remains poorly defined. Moreover, it remains to be determined if histone crotonylation is physiologically significant and functionally distinct from or redundant to histone acetylation. Here we present evidence that class I histone deacetylases (HDACs) rather than sirtuin family deacetylases (SIRTs) are the major histone decrotonylases, and that histone crotonylation is as dynamic as histone acetylation in mammalian cells. Notably, we have generated novel HDAC1 and HDAC3 mutants with impaired HDAC but intact HDCR activity. Using these mutants we demonstrate that selective HDCR in mammalian cells correlates with a broad transcriptional repression and diminished promoter association of crotonylation but not acetylation reader proteins. Furthermore, we show that histone crotonylation is enriched in and required for self-renewal of mouse embryonic stem cells.

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Cell Line
  • Gene Expression
  • Histone Deacetylase Inhibitors / metabolism
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Histones / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Lysine / metabolism
  • Mice
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Niacinamide / pharmacology
  • Sirtuins / metabolism
  • Transcription Factors / metabolism*
  • Transcription, Genetic*


  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Mutant Proteins
  • Transcription Factors
  • Niacinamide
  • trichostatin A
  • Sirtuins
  • Histone Deacetylases
  • Lysine