Tracking DOT1L Methyltransferase Activity by Stable Isotope Labelling Using a Selective Synthetic Co-Factor

Histone methylation is a post-translational modification (PTM) regulating gene expression. We developed an isotopically labelled analogue of co-factor S-adenosyl-L-methionine (13CD3-BrSAM), with selectivity for the histone lysine methyltransferase DOT1L, permitting tracking of methylation activity by mass spectrometry (MS). This concept could be applied to other methyltransferases, linking PTM discovery to enzymatic mediators.