Rapid Response and Slow Recovery of the H3K4me3 Epigenomic Marker in the Liver After a Light-Mediated Phase Advance of the Circadian Clock

Mammalian tissues display circadian rhythms in which transcription levels rise and fall throughout a 24-hour day. These rhythms include histone modifications. Here we asked whether an advance of the light-dark cycle could alter rhythms in the liver epigenome at the H3K4me3 (trimethylation of lysine 4 on histone 3) modification, which is found at active and poised gene promoters. H3K4me3 levels were first measured at 4-time points (Zeitgeber Time [ZT] 3, 8, 15, and 20) during a normal 12L:12D light:dark cycle. Peak levels were observed during the early dark phase at ZT15, and dropped to low levels around lights-on (ZT0) between ZT20 and ZT3. A six-hour phase advance at ZT18 (new lights-on after only 6 h of darkness) led to a transient extension of peak H3K4me3 levels. Although locomotor activity re-entrained within a week after the phase advance, H3K4me3 rhythms failed to do so with peak levels remaining in the light phase at the one-week recovery time point. Eight weekly phase advances, with one-week recovery times between each phase advance, also led to disruption of the liver circadian epigenome. A model to explain these results is offered. 20 H3K4me3 ChIP-Seq samples were analyzed with 1 Input IgG ChIP-Seq control. Each sample represents ChIP-Seq performed on four mouse livers and then the four samples pooled.