Abstract
Circadian rhythms orchestrate organismal physiology and behavior in order to anticipate daily changes in the environment. Virtually all cells have an internal rhythm that is synchronized every day by Zeitgebers (environmental cues). The synchrony between clocks within the animal enables the fitness and the health of organisms. Conversely, disruption of rhythms is linked to a variety of disorders: aging, cancer, metabolic diseases, and psychological disorders among others. At the cellular level, mammalian circadian rhythms are built on several layers of complexity. The transcriptional-translational feedback loop (TTFL) was the first to be described in the 90s. Thereafter oscillations in epigenetic marks highlighted the role of chromatin state in organizing the TTFL. More recently, studies on the 3D organization of the genome suggest that genome topology could be yet another layer of control on cellular circadian rhythms. The dynamic nature of genome topology over a solar day implies that the 3D mammalian genome has to be considered in the fourth dimension-in time. Whether oscillations in genome topology are a consequence of 24 h gene-expression or a driver of transcriptional cycles remains an open question. All said and done, circadian clock-gated phenomena such as gene expression, DNA damage response, cell metabolism and animal behavior—go hand in hand with 24 h rhythms in genome topology.
Highlights
Our environment displays multiple cycles with different periodicities, from ultradian (period less than 24 h, as for tides), circadian (around 24 h, as for a solar day), and infradian (period greater than 24 h, as for seasons)
Our environment displays multiple cycles with different periodicities, from ultradian, circadian, and infradian
The analysis revealed that core clock loci tend to contact fewer genomic elements but are more dynamic
Summary
Our environment displays multiple cycles with different periodicities, from ultradian (period less than 24 h, as for tides), circadian (around 24 h, as for a solar day), and infradian (period greater than 24 h, as for seasons). The molecular mechanism of the core clock involves several layers of complexity orchestrated by transcriptional activators and repressors and chromatin state remodeling factors. Once in the nucleus PER-CRY complexes interact with BMAL1-CLOCK to inhibit transcription including their own expression (Lee et al, 2001).
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