Formaldetected: Application of 1H- and 1D 13C HSQC NMR spectroscopy methods for monitoring the activity of a 2-oxoglutarate dependent histone Nε-methyllysine demethylase (JMJD2E) enabled the in situ quantitative analysis of the different components of the reaction, including the direct observation of hydrated formaldehyde resulting from enzyme-catalysed demethylation.