Lysine Methylation Signaling: Detection, Quantification, and Substrate Discovery

Lysine methylation modulates the function of histone and non-histone proteins, and the enzymes that add or remove lysine methylation—lysine methyltransferases (KMTs) and lysine demethylases (KDMs), respectively—are frequently mutated and dysregulated in human diseases. To gain more insight into lysine methylation signaling, we face two obstacles. First, it is difficult to detect and quantify lysine methylation on non-histone proteins. Second, it remains challenging to connect KMTs and KDMs with their substrates. I will discuss our recent efforts to overcome these obstacles by quantifying lysine methylation in cancer cells and discovering substrates of PRDM9, ASH1L, and SETMAR.