biostudies-literatureZheng QNIDA NIH HHSNIMH NIH HHSNCI NIH HHSNIGMS NIH HHSNIH HHS974-982https://www.ebi.ac.uk/biostudies/studies/S-EPMC11754111biostudies-literatureUnknown637(8047)Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression^1-3. We previously demonstrated that serotonylation^4-10 and dopaminylation^9,11-13 of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour. We found that H3Q5his, in contrast to H3Q5ser, inhibits the binding of WDR5, a core member of histone H3 Lys4 (H3K4) methyltransferaNatureBidirectional histone monoaminylation dynamics regulate neural rhythmicity.PMC11754111R35 GM150676R01 GM086868R01 MH116900P30 CA013330S10 OD030286P30 CA008748R37 GM086868R01 DA056595T32 DA007135P50 CA192937P01 DA047233R35 GM138386Wu JShen LWeekley BHStransky SZhang NWang HCunningham AMThompson REMolina HDavid YSidoli SVinson DAZhao SDierdorff LVostal LUpad AZhang BLi HFulton SLKong LDutta SChan JCChen MZheng QRamakrishnan ADi Salvo GMuir TWBastle RMMaze IfalseBidirectional histone monoaminylation dynamics regulate neural rhythmicity.Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression^1-3. We previously demonstrated that serotonylation^4-10 and dopaminylation^9,11-13 of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour. We found that H3Q5his, in contrast to H3Q5ser, inhibits the binding of WDR5, a core member of histone H3 Lys4 (H3K4) methyltransfera2025-01-01T00:00:00Z2025 Jan2026-06-02T13:15:04.458Z2025-04-19T18:19:32.693ZS-EPMC117541113977984910.1038/s41586-024-08371-3