Large-scale global identification of protein lysine methylation in vivo

Lysine methylation mediated by methyltransferase enzymes is present on multiple proteins throughout the cell; however, methods to uncover and characterize global protein lysine methylation patterns do not readily exist. Here we developed pan-specific methyl lysine antibodies that we utilized in immunoprecipitation experiments coupled with mass spectrometry to yield one of the first large-scale surveys of protein lysine methylation in vivo. In total, 552 different lysine methylation sites were determined, making this one of the most comprehensive global studies published to date. The large majority of these sites have not been yet reported. These sites showed significantly enriched sequence motifs and resided in proteins that are involved in diverse biological processes, particularly in chromatin organization. Our data provide a comprehensive view of lysine methylation in human cells and a powerful resource to facilitate investigations into the function of lysine methylation on non-histone proteins.