Histone H3 tail clipping regulates gene expression

Nat Struct Mol Biol. 2009 Jan;16(1):17-22. doi: 10.1038/nsmb.1534. Epub 2008 Dec 14.


Induction of gene expression in yeast and human cells involves changes in the histone modifications associated with promoters. Here we identify a histone H3 endopeptidase activity in Saccharomyces cerevisiae that may regulate these events. The endopeptidase cleaves H3 after Ala21, generating a histone that lacks the first 21 residues and shows a preference for H3 tails carrying repressive modifications. In vivo, the H3 N terminus is clipped, specifically within the promoters of genes following the induction of transcription. H3 clipping precedes the process of histone eviction seen when genes become fully active. A truncated H3 product is not generated in yeast carrying a mutation of the endopeptidase recognition site (H3 Q19A L20A) and gene induction is defective in these cells. These findings identify clipping of H3 tails as a previously uncharacterized modification of promoter-bound nucleosomes, which may result in the localized clearing of repressive signals during the induction of gene expression.

MeSH terms

  • Endopeptidases / metabolism*
  • Gene Expression Regulation, Fungal*
  • Genes, Fungal
  • Histones / metabolism*
  • Promoter Regions, Genetic*
  • RNA, Fungal / genetics
  • RNA, Messenger / genetics
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription, Genetic


  • Histones
  • RNA, Fungal
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Endopeptidases
  • histone proteases