The MTase-Glo Assay is a bioluminescence-based assay that can be used to monitor the activities of methyltransferases (MTases) and their modulation by small molecules in a wide range of plate formats. The assay is well suited for high-throughput screening applications. The assay monitors formation of the reaction product S-adenosyl homocysteine (SAH) and can detect changes in activity of a broad range of methyltransferases, including DNA, protein, RNA and small molecule methyltransferases. The MTase-Glo Assay can be used for all classes of protein methyltransferases (lysine and arginine) and with different types of substrates (peptides, large proteins and even nucleosomes) to determine the specificity of these enzymes and their substrate requirements. After the methyltransferase reaction is complete, the MTase-Glo Reagent is added to convert SAH to ADP. The MTase-Glo Detection Solution is then added to convert ADP to ATP, which is detected via a coupled luciferase reaction. Luminescence is measured using a plate-reading luminometer and can be correlated to SAH concentration using an SAH standard curve. The half-life of the luminescent signal is greater than 4 hours. This extended signal half-life eliminates the need for luminometers with injectors and allows batch-mode processing of multiple plates.