Monoamines such as the neurotransmitter serotonin have been shown to form covalent bonds with certain proteins via transamidation by the TGM2 enzyme. Here, Ian Maze and colleagues show that TGM2 can catalyse serotonylation on Gln5 of histone H3 and this mark occurs in the presence of the active histone mark H3K4me3. The dual mark H3K4me3Q5ser is enriched in brain and gut (organs where the bulk of serotonin is produced) and correlates with active gene expression. The findings indicate a role for serotonin in mediating gene expression in addition to its known roles in neurotransmission and cellular signalling.
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