Abstract
Transglutaminases (TGs) were originally discovered to catalyze protein-protein crosslinking by forming isopeptide bonds between the side chains of lysine and glutamine. Recently, TGs have been found to mediate the bioconjugation between protein glutamines and monoamine metabolites (such as serotonin, dopamine, and histamine), which is termed 'monoaminylation'. Monoaminylation on core histones, installed by human transglutaminase 2 (TG2), is an emerging epigenetic mark that plays a significant role in regulating cellular gene transcription. Unlike other histone post-translational modifications, the dynamics of monoaminylation (including its installation, removal, and replacement) are solely regulated by TG2. Here, we review the most recent advances in TG2-mediated histone monoaminylation (including serotonylation, dopaminylation, and histaminylation), focusing on its novel biochemical basis and epigenetic functions in pathophysiology.