Methyltransferases (MTases) have mostly been known to target lysine residues as post-translational protein modification. However, some are proven to target histidine residues. Histidine can be methylated on the π- or τ-nitrogen. So far, only five mammalian proteins have been identified as substrate of such MTase. During my PhD, I will focus on the identification of histidine MTases and their substrates as well as the dynamic regulation and function.