Temporal transcriptomics suggest that twin-peaking genes reset the clock

Abstract

The mammalian suprachiasmatic nucleus (SCN) drives daily rhythmic behavior and physiology, yet a detailed understanding of its coordinated transcriptional programmes is lacking. To reveal the finer details of circadian variation in the mammalian SCN transcriptome we combined laser-capture microdissection (LCM) and RNA-seq over a 24 hr light / dark cycle. We show that 7-times more genes exhibited a classic sinusoidal expression signature than previously observed in the SCN. Another group of 766 genes unexpectedly peaked twice, near both the start and end of the dark phase; this twin-peaking group is significantly enriched for synaptic transmission genes that are crucial for light-induced phase shifting of the circadian clock. 341 intergenic non-coding RNAs, together with novel exons of annotated protein-coding genes, including Cry1, also show specific circadian expression variation. Overall, our data provide an important chronobiological resource (www.wgpembroke.com/shiny/SCNseq/) and allow us to propose that transcriptional timing in the SCN is gating clock resetting mechanisms.The daily cycles of life in mammals are driven by a small region of the brain called the suprachiasmatic nucleus (or SCN). The SCN receives signals from sunlight and other environmental factors to help coordinate most aspects of daily biological activity and behaviour. To work correctly, it is essential that the SCN switches certain genes on and off at exactly the right time. However, many questions remain over the identity of these genes and how their levels of activity change during a 24-hour period.When a gene is active (or “being expressed”), it is used as a template to build the molecules of RNA that are needed to make proteins and to help to control how cells work. Pembroke et al. have now sequenced the RNA molecules made in the SCN of mice (which plays the same role as the equivalent human brain region) over a 24-hour period. The mice spent half of each day in the light, and half in the dark. This revealed that the expression levels of over a quarter of all the genes that are found in the SCN fluctuate over a 24-hour period. One particular group of genes peak in activity twice a day; Pembroke et al. suggest that these genes are important for controlling how an animal can adjust its body clock to light.Further research is now needed to find out which of the newly discovered fluctuating genes play the most important roles in daily activity rhythms, and which might play a part in disease.