Abstract
Author SummaryIn mammalian organs such as the liver, many metabolic and physiological processes occur preferentially at specific times during the 24-hour daily cycle. The timing of these rhythmic functions depends on a complex interplay between the endogenous circadian clock and environmental timing cues relayed through the master circadian clock in the suprachiasmatic nucleus, or via feeding rhythms. These rhythms can be implemented on several regulatory levels, and here we aimed at a better understanding of the transcriptional and epigenetic changes that regulate diurnal rhythms. We performed genome-wide analysis of the locations of RNA polymerase II (Pol II) and the epigenetic histone modifications H3K4me3 and H3K36me3 at specific times of day, relating these data to mRNA expression levels. Our analyses show that Pol II transcriptional rhythms are biphasic in mouse liver, having predominant peak activities in the morning and evening. Moreover, dynamic changes in histone marks lag transcription rhythms genome-wide, indicating that the epigenetic landscape can be remodeled during the 24-hour cycle. Finally, a quantitative analysis of temporal Pol II and mRNA accumulation profiles indicates that posttranscriptional regulation significantly contributes to the amplitude and phase of mRNA accumulation profiles. While many studies have analyzed how transcription and chromatin states are modified during irreversible cell differentiation processes, our work highlights how these states can evolve reversibly in a system exhibiting periodicity in time.
Highlights
In most mammalian organs, widespread diurnal rhythms in mRNA expression underlie the temporal compartmentalization of cellular and physiological processes [1]
Our analyses show that Pol RNA polymerase II (II) transcriptional rhythms are biphasic in mouse liver, having predominant peak activities in the morning and evening
Analysis of chromatin immuno-precipitation (ChIP)-seq profiles for polymerase II (Pol II) (RPB2 subunit), H3K4me3, and H3K36me3 in mouse liver revealed that Pol II occupancy correlated well with known transcription phases of core clock and clock-control genes (Figures 1 and S1)
Summary
Widespread diurnal rhythms in mRNA expression underlie the temporal compartmentalization of cellular and physiological processes [1]. Studies on many individual genes have shown that circadian transcription is accompanied by temporally varying epigenetic modifications [9,15,16,17,18,19], but it is only recently that this question is being addressed genome-wide [20]. Such studies are important as they can reveal the relationships between the kinetics of transcription and related histone modifications in a system that returns to the same state every 24 h
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