Lysine succinylation and lysine malonylation in histones

Mol Cell Proteomics. 2012 May;11(5):100-7. doi: 10.1074/mcp.M111.015875. Epub 2012 Mar 4.

Abstract

Histone protein post-translational modifications (PTMs) are significant for gene expression and DNA repair. Here we report the identification and validation of a new type of PTM in histones, lysine succinylation. The identified lysine succinylated histone peptides were verified by MS/MS of synthetic peptides, HPLC co-elution, and isotopic labeling. We identified 13, 7, 10, and 7 histone lysine succinylation sites in HeLa, mouse embryonic fibroblast, Drosophila S2, and Saccharomyces cerevisiae cells, respectively. We demonstrated that this histone PTM is present in all eukaryotic cells we examined. Mutagenesis of succinylation sites followed by functional assays implied that histone lysine succinylation can cause unique functional consequences. We also identified one and two histone lysine malonylation sites in HeLa and S. cerevisiae cells, respectively. Our results therefore increase potential combinatorial diversity of histone PTMs and suggest possible new connections between histone biology and metabolism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Cell Line
  • Conserved Sequence
  • Drosophila
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism*
  • Malonates / metabolism*
  • Mice
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Phenotype
  • Protein Processing, Post-Translational*
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Succinates / metabolism*
  • Tandem Mass Spectrometry

Substances

  • Histones
  • Malonates
  • Peptide Fragments
  • Saccharomyces cerevisiae Proteins
  • Succinates
  • Lysine