Temporal transcriptomics suggest that twin-peaking genes reset the clock

Pembroke, William G; Babbs, Arran; Davies, Kay E.; Ponting, Chris P.; Oliver, Peter L.

doi:10.7554/elife.10518

Cited by 79 publications

(84 citation statements)

References 54 publications

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“…Circadian clocks can generate rhythms with periods other than 24 h. Recent work has revealed two peaks of activation per circadian cycle in a subset of genes in the mammalian suprachiasmatic nucleus (Pembroke et al, 2015). 12-h oscillations have also been observed in peripheral mammalian tissues, including the liver (Hughes et al, 2009;Cretenet et al, 2010), bone marrow (Chen et al, 2000) and testis (Liu et al, 2007) in mice.…”

Section: Introductionmentioning

confidence: 99%

Frequency doubling in the cyanobacterial circadian clock

Martins

Das

Antunes

et al. 2016

Molecular Systems Biology

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Organisms use circadian clocks to generate 24‐h rhythms in gene expression. However, the clock can interact with other pathways to generate shorter period oscillations. It remains unclear how these different frequencies are generated. Here, we examine this problem by studying the coupling of the clock to the alternative sigma factor sigC in the cyanobacterium Synechococcus elongatus. Using single‐cell microscopy, we find that psbAI, a key photosynthesis gene regulated by both sigC and the clock, is activated with two peaks of gene expression every circadian cycle under constant low light. This two‐peak oscillation is dependent on sigC, without which psbAI rhythms revert to one oscillatory peak per day. We also observe two circadian peaks of elongation rate, which are dependent on sigC, suggesting a role for the frequency doubling in modulating growth. We propose that the two‐peak rhythm in psbAI expression is generated by an incoherent feedforward loop between the clock, sigC and psbAI. Modelling and experiments suggest that this could be a general network motif to allow frequency doubling of outputs.

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Section: Introductionmentioning

confidence: 99%

Frequency doubling in the cyanobacterial circadian clock

Martins

Das

Antunes

et al. 2016

Molecular Systems Biology

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“…Because more and more cycling genes have been identified, the collection and integration of the data is helpful for further experimental consideration. Previously, four major databases were developed for circadian genes, including DIURNAL (23), CircaDB (29), SCNseq (30) and Bioclock (31–33). The DIURNAL database maintains circadian microarray data for three plants, including Arabidopsis thaliana , poplar and rice (23).…”

Section: Introductionmentioning

confidence: 99%

OUP accepted manuscript

Shui

Zhang

et al. 2016

Nucleic Acids Research

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We report a database of circadian genes in eukaryotes (CGDB, http://cgdb.biocuckoo.org), containing ∼73 000 circadian-related genes in 68 animals, 39 plants and 41 fungi. Circadian rhythm is ∼24 h rhythm in behavioral and physiological processes that exists in almost all organisms on the earth. Defects in the circadian system are highly associated with a number of diseases such as cancers. Although several databases have been established for rhythmically expressed genes, a comprehensive database of cycling genes across phyla is still lacking. From the literature, we collected 1382 genes of which transcript level oscillations were validated using methods such as RT-PCR, northern blot and in situ hybridization. Given that many genes exhibit different oscillatory patterns in different tissues/cells within an organism, we have included information regarding the phase and amplitude of the oscillation, as well as the tissue/cells in which the oscillation was identified. Using these well characterized cycling genes, we have then conducted an orthologous search and identified ∼45 000 potential cycling genes from 148 eukaryotes. Given that significant effort has been devoted to identifying cycling genes by transcriptome profiling, we have also incorporated these results, a total of over 26 000 genes, into our database.

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“…73636034, probe RP_050825_02_B04coronal). A recent study also found that Hrh3 expression varies rhythmically in the SCN with peak levels found in the late day (Pembroke et al 2015). There is strong evidence that HA can phase-shift the circadian neural activity rhythms in rodent SCN slices (Cote and Harrington 1993;Meyer et al 1998;Biello 2009;Kim et al 2015).…”

Section: Discussionmentioning

confidence: 89%

Possible use of a H3R antagonist for the management of nonmotor symptoms in the Q175 mouse model of Huntington's disease

Whittaker

Wang

Loh

et al. 2017

Pharmacology Res & Perspec

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Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder characterized by motor as well as nonmotor symptoms for which there is currently no cure. The Q175 mouse model of HD recapitulates many of the symptoms identified in HD patients including disruptions of the sleep/wake cycle. In this study, we sought to determine if the daily administration of the histamine‐3 receptor (H3R) antagonist/inverse agonist 6‐[(3‐cyclobutyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepin‐7‐yl)oxy]‐N‐methyl‐3‐pyridinecarboxamide hydrochloride (GSK189254) would improve nonmotor symptoms in the Q175 line. This class of drugs acts on autoreceptors found at histaminergic synapses and results in increased levels of histamine (HA). HA is a neuromodulator whose levels vary with a daily rhythm with peak release during the active cycle and relatively lower levels during sleep. H3Rs are widely expressed in brain regions involved in cognitive processes and activation of these receptors promotes wakefulness. We administered GSK189254 nightly to homozygote and heterozygote Q175 mice for 4 weeks and confirmed that the plasma levels of the drug were elevated to a therapeutic range. We demonstrate that daily treatment with GSK189254 improved several behavioral measures in the Q175 mice including strengthening activity rhythms, cognitive performance and mood as measured by the tail suspension test. The treatment also reduced inappropriate activity during the normal sleep time. The drug treatment did not alter motor performance and coordination as measured by the challenging beam test. Our findings suggest that drugs targeting the H3R system may show benefits as cognitive enhancers in the management of HD.

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Temporal transcriptomics suggest that twin-peaking genes reset the clock

Cited by 79 publications

References 54 publications

Frequency doubling in the cyanobacterial circadian clock

Frequency doubling in the cyanobacterial circadian clock

OUP accepted manuscript

Possible use of a H3R antagonist for the management of nonmotor symptoms in the Q175 mouse model of Huntington's disease

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