Lysine succinylation and lysine malonylation in histones

摘要

Histone protein post-translational modifi cations (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 (MEF), Drosophila S2 and S. cerevisiae cells, respectively. We demonstrate that this histone PTM is present in all eukaryotic cells we examined. Mutagenesis of succinylation sites followed by functional assays implies that histone lysine succinylation can cause unique functional consequences. We also identified 1 and 2 histone lysine malonylation sites in Hela and S. cerevisiae cells, respectively. Our results therefore increas e potential combinatorial diversity of histone PTMs and suggest possible new connec tions between histone biology and metabolism.