Fig. 3: Neural H3Q5 monoaminylations are diurnally rhythmic.

a, RNA-seq analysis of the mouse TMN across ZT (JTKcycle, P_adj < 0.05). n = 3 biological replicates per timepoint. b, Ontology analysis (P < 0.05) of RNA-seq data from a. c, Known circadian genes identified in a. d, CUT&RUN–seq enrichment for H3K4me3Q5his across ZT at genic loci in TMN. n = 3 biological replicates per timepoint (JTKcycle, P_adj < 0.05). e, Ontology analysis (P < 0.05) comparing enrichment of CLOCK-mediated gene targets for genes displaying rhythmic H3K4me3Q5his only versus circadian genes not displaying rhythmic H3K4me3Q5his and/or gene expression. f, The average signal intensity ±500 bp from the transcription start site (TSS) across ZT for H3 monoaminylations and WDR5. g, The average signal intensity ±500 bp from the TSS across ZT for H3K4me3Q5his and H3K4me3. h, IGV tracks for Per2 across ZT for H3 monoaminylations versus WDR5 versus H3K4me2/3. i, Overlap of rhythmic H3 monoaminylation genes with WDR5-enriched genes at ZT16 (left), and ontology analysis (P < 0.05) comparing enrichment of CLOCK-mediated gene targets for genes displaying rhythmic H3 monoaminylation versus WDR5 enrichment at ZT16 (right). j, Locomotor activity in mice treated with zolpidem (n = 12 mice) versus vehicle (n = 13 mice) during their active phase. Statistical analysis was performed using repeated-measures two-way ANOVA (main effects of interaction, time × zolpidem: P < 0.0001, F_7,161 = 11.98) with Tukey’s multiple-comparison test; significant post hoc comparisons (vehicle (veh.) versus zolpidem) are noted (1 h: ****P < 0.0001; 2 h: *P = 0.0412). k, CUT&RUN–seq enrichment for H3 monoaminylations and WDR5 at ZT20 after treatments with zolpidem versus vehicle (at ZT12) at genic loci in TMN. n = 3 biological replicates per timepoint. l, IGV tracks for Per2 and Clock at ZT20 for H3 monoaminylations and WDR5 after treatments with zolpidem versus vehicle (at ZT12) at genic loci in the TMN. Data are mean ± s.e.m.

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