Arg-C Ultra simplifies histone preparation for LC-MS/MS

Using mammalian histone extract, we demonstrate that Arg-C Ultra facilitates histone preparation for LC-MS/MS. We show the performance of Arg-C Ultra in terms of digestion specificity, number of modified forms identified, and yield of quantitative information compared with standard Arg-C and trypsin digestion combined with chemical derivatization with trimethylacetic anhydride. We show that chemical derivatization at the peptide level, i.e., after Arg-C Ultra digestion, is still necessary to improve the quantification of short histone peptidoforms as well as positional isomers.