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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 true nature of circadian variation in the mammalian SCN transcriptome we combined laser-capture microdissection (LCM) and RNA-Seq over a 24-hour 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. 342 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE72095 | GEO | 2015/11/03

SECONDARY ACCESSION(S): PRJNA292917

REPOSITORIES: GEO

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Temporal transcriptomics suggest that twin-peaking genes reset the clock

Project description: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 true nature of circadian variation in the mammalian SCN transcriptome we combined laser-capture microdissection (LCM) and RNA-Seq over a 24-hour 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. 342 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. Pooled dissected tissue of the suprachiasmatic nucleus from five adult male mice provided one of three replicates for each of six time points over a 12:12 light/dark (LD) cycle (ZT2, 6, 10, 14, 18 and 22). Each biological replicate was sequenced over 3 separate lanes using Illumina HiSeq.

2015-11-03 | E-GEOD-72095 | biostudies-arrayexpress

Light-induced Changes in the Suprachiasmatic Nucleus Transcriptome Regulated by the ERK/MAPK Pathway

Project description:The mammalian master circadian pacemaker within the suprachiasmatic nucleus (SCN) maintains tight entrainment to the 24 hr light/dark cycle via a sophisticated clock-gated rhythm in the responsiveness of the oscillator to light. Intriguingly, entrainment is not merely a passive response, instead the internal oscillator responds and adjust its own timing to entrainment signals discriminating the time of day. For example, exposure to brief light pulses in the first and final hours of the subjective generate circadian phase delays and advances respectively; whereas similar photic pulses during the subjective day does not modify the phase. A central event in this light entrainment process appears to be the rapid induction of gene expression via the ERK/MAPK pathway. We used microarray-based expression profiling of the suprachiasmatic nucleus to examine the role of MAPK signaling in the light-evoked transcriptional response. We focused on three circadian timepoints that define the unique, clock-time delimited response properties of the SCN to light: the subjective day, early subjective night, and late subjective night.

2021-03-24 | GSE165799 | GEO

Diurnal gene expression in the retina of a mouse model of diabetic retinopathy

Project description:The mammalian retina contains an endogenous circadian clock system, located in various cell types. This system enables timing of a broad range of essential retinal functions to anticipate daily changes in environmental lighting conditions. Furthermore, the circadian clocks appear to promote retinal health. A leading cause of blindness in developed countries is diabetic retinopathy. While it is clear that diabetes affects the master clock and its circadian output in the SCN, the effect of diabetic retinopathy on the retinal clock system is unknown. To investigate the influence of diabetic retinopathy on circadian regulation of the retina at a genome-wide level, microarray analysis was used to compare retinal transcriptomes between light- and dark-adapted non-diabetic and diabetic mice.

2021-09-05 | GSE151350 | GEO

Comprehensive and cell-type-based analysis of microRNA profiles and functions in mouse suprachiasmatic nucleus

Project description:Circadian rhythm governs a variety of biological processes in essentially all living organisms and microRNAs have been found to play important roles in the post-transcriptional regulation of circadian clocks. However, the microRNA expression profile in mouse central circadian clock – suprachiasmatic nucleus (SCN) is lacking. In this study, we systematically profiled microRNAs in mouse SCN and SCN subtype neurons by high sensitive small RNA sequencing and examined their potential circadian functions. We found that a large fraction of known microRNAs are SCN-specific and 20 of them are also oscillated significantly. Predicted targets of these 20 microRNAs were enriched in circadian rhythm pathway as well. Integrated analysis of microRNA and mRNA revealed 3 clock-related functional modules, demonstrating the regulation roles of miR-24, miR-30, miR-7a, miR-7b, miR125a and miR125b in SCN. Furthermore, we observed distinct microRNA profiles in SCN subtype neurons with divergent regulatory functions, which correlated with their differential spatial distribution. In addition, we also identified a proportion of light-response microRNAs in SCN, one of which was miR-7a. Further experiments showed that miR-7a directly target fos and regulated its translation in SCN. All these observations indicate important circadian regulation roles of microRNA in central circadian clock.

2021-08-18 | GSE133051 | GEO

Expression data from Arabidopsis thaliana seedlings

Project description:Light pulses at the end of the day or night be able to control the phase of the circadian clock. Pulses in the middle of the night has not effect on the circadian oscilations. To understand how the circadian clock gate the light signal in the middle of the night we used microarrays to characterize the light effect in the whole expression profile. Plants of Arabidopsis thalina (Columbia ecotype) were grown in 12/12 light/dark cicles for 15 days and then were tranfer to continuous dark . Plants were slplit in two groups. First group recieved 1hr light pulse in the middle of the night (Night treatment), second group recieve 1hr light pulse in the middle of the subjective day (Day Treatment). Samples of both groups were collected without light pulse named as a control.

2013-08-02 | E-GEOD-46621 | biostudies-arrayexpress

Timed Exercise and Clocks: Does a Minimally Functional Suprachiasmatic Clock Support 24h Behavioral Rhythms?

Project description:The brain’s suprachiasmatic nucleus (SCN) is the master clock driving circadian rhythms in mammals. Vasoactive intestinal polypeptide (VIP) and its cognate receptor, VPAC2, are expressed in SCN neurons and mice with genetically targeted deletion of VPAC2 (Vipr2 -/-animals) show aberrant resetting to light, abnormal behavioral rhythms, and diminished SCN clock gene expression. Timed daily access to a running-wheel (scheduled voluntary exercise; SVE) promotes Vipr2 -/- SCN clock cell synchrony and 24h behavioral rhythms. We hypothesized that timed exercise alters the SCN transcriptome. Here, in control (Vipr2+/+) and Vipr2-/- mice under freely exercising and SVE conditions, RNAseq and qRT-PCR were used to measured gene expression of laser-dissected SCN. Compared to Vipr2+/+ mice, hundreds of genes were differentially expressed in the SCN from Vipr2-/- mice rhythmic in the freely exercising condition. Unexpectedly, SVE did not promote a Vipr2+/+-like SCN transcriptome in Vipr2-/- mice and many transcripts involved in SCN function including Avp, C1ql3, Gpr176, Prok2, Sst, Per2, and Nr1d1 remained dysregulated in the SVE condition. By contrast, circadian oscillators in the liver and lung were mostly intact in Vipr2-/- mice. This study indicates that marked molecular deficits in the SCN are sustained in behaviorally rhythmic Vipr2-/- mice, raising the possibility that a minimal functional SCN circadian clock can underpin whole animal rhythms.

2023-01-20 | GSE207992 | GEO

PRL-1 selectively dephosphorylates TIMELESS

Project description:The timing of behavior under natural light-dark conditions is a function of circadian clocks and photic input pathways. Yet a mechanistic understanding of how these pathways collaborate in animals is lacking. Here we demonstrate in Drosophila that the Phosphatase of Regenerating Liver-1 (PRL-1) sets period length and behavioral phase gated by photic signals. PRL-1 knockdown in PDF clock neurons dramatically lengthens circadian period. PRL-1 mutants exhibit allele-specific interactions with the light- and clock-regulated gene timeless (tim). Moreover, we show that PRL-1 promotes TIM accumulation and dephosphorylation. Interestingly, the PRL-1 mutant period lengthening is suppressed in constant light and PRL-1 mutants display a delayed phase under short, but not long, photoperiod conditions. Thus, our studies reveal that PRL-1 dependent dephosphorylation of TIM is a core mechanism of the clock that sets period length and phase in darkness, enabling the behavioral adjustment to changing day-night cycles.

2020-11-11 | PXD020986 | Pride

Regulatory logic of the coupled diurnal and feeding cycles in the mouse liver [array]

Project description:In mammals, the circadian clock controls behavioral, physiological and cellular rhythms. Part of this daily variation is controlled by transcription-translation feedback loops in sync with the light-dark phase. On the other hand, daily rhythms in expression of a multitude of genes are related to nutrient-response cycles. Time-resolved mapping of DNase I hypersensitive sites (DHS) throughout the day can identify details of the regulatory interplay between metabolism and the internal clock at a molecular level. Here, we report a genome-wide analysis of mammalian DHS using high‐throughput sequencing of DNase tags from mouse liver with a resolution of 4 h (12 h light/12 h dark). Among the 65’000 DHS sites identified, a significant proportion of distal DHS showed a diurnal cycle, suggesting a fine regulation of oscillating genes by enhancers, which we seek to understand better. Using PolII and H3K27ac ChIP-seq, we characterize the DHS and study the dynamics of each mark in wild-type and Bmal1-KO mice. We use the sequence motif content of each DHS and a linear regression model to explain DHS temporal behaviour in terms of phase and amplitude. We monitor the temporal expression of target genes in order to understand the phase-specific regulation in the circadian context. Interestingly, DHS associated with circadian genes tend to be time-correlated with expression, Pol II and H3K27ac marks. The Bmal1-KO phenotype in light-dark conditions show a proportion of DHS with circadian rhythms associated with transcription factors related to metabolism, due to food entrainment and systemic cues.

2016-12-31 | GSE60577 | GEO

Circadian regulation in rat Lung

Project description:Circadian rhythms are oscillations with a periodicity of 24 hours that are controlled by an endogenous clock and are observed in virtually all aspects of mammalian function from expression of genes to complex physiological processes. The master clock is present in the suprachiasmatic nucleus (SCN) in the anterior part of the hypothalamus and controls peripheral clocks present in other parts of the body . Although much is known about the mechanism of the central clock in the SCN, the regulation of clocks present in peripheral tissues is still unclear. This study is designed to examine fluctuations in gene expression in lungs within the 24 hour circadian cycle in normal animals. The objectives of this study is to identify and analyze circadian oscillation in gene expression in lungs, and to identify the role of circadian regulation in coordinating the functioning of this dynamic organ. Fifty-four male normal Wistar rats (250-350 g body weight) were housed in a strictly controlled stress free environment with light:dark cycles of 12 hr:12hr. Three animals were sacrificed at each of 18 selected time points within the 24 hour cycle. RNA was prepared from lungs for gene arrays. Time point designations reflect time after lights on in hours.

2010-12-20 | E-GEOD-25612 | biostudies-arrayexpress

RNA-Seq Analysis of Wild Type and Scn5aΔ/+ left ventricle at dark:light and light:dark phase transitions

Project description:We investigated differences in gene expression in left ventricular tissue from WT and ΔKPQ (Scn5aΔ/+) mice. Tissue was collected diurnally at the phase transitions from dark to light (D:L) and light to dark (L:D). We employed RNAseq (Novogene) to examine potential variances between the two strains of mice, as well as, any differences in expression at the two time points. RNAseq provided a snapshot of gene expression which revealed an intact molecular clock for both strains. Previous studies have demonstrated circadian peak or trough at the light phase changes in cardiac tissue in mice for many core molecular clock components. Similar to these studies both strains demonstrated a significant difference in expression between core molecular clock genes Bmal1, Clock, Per1, Per2, Per3 assessed at the phase transitions. This assessment revealed 39 diurnally expressed genes. To our surprise, only 6 genes were differently expressed between the two strains of mice.

2020-03-06 | GSE146405 | GEO

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