Clock rescue in the brain restores 12- and 24- hour rhythms in the liver
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE30411 | GEO | 2012/06/01
SECONDARY ACCESSION(S): PRJNA143375
REPOSITORIES: GEO
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Project description:Circadian profiling was performed in mouse livers from three different genotypes/treatments: Wildtype, Clock mutant, and brain-specific Clock rescue. Rescuing Clock specifically in the brain partially rescued robust circadian and harmonic rhythms. Samples were collected every 2 hours for 48 hours from 2-4 mice per time point; samples were pooled and analyzed using Affymetrix Mouse Exon arrays, analyzed at the gene level.
2012-05-31 | E-GEOD-30411 | biostudies-arrayexpress
Project description:Circadian clocks drive 24-h rhythms of physiology and behavior. The circadian clock of hepatocytes has been shown to regulate glucose metabolism, and we were interested if rescuing liver clock function can reverse metabolic impairments in hyperphagic/obese Clock-D19 mutant mice. We compared transcripomte regulation in livers (at Zeitgeber time ZT10) of wild-type (C57BL/6J) and Clock-D19 mice and Clock-D19 mice with genetic rescue of liver clock function using hydrodynamic tail vein injection of a WT-CLOCK expression plasmid
2017-03-31 | GSE94838 | GEO
Project description:Circadian (~24 hour) clocks exist in almost all types of living organism and play a fundamental role in regulating daily physiological and behavioural processes. The transcription factor BMAL1 (ARNTL) is thought to be one of the principal drivers of the molecular clock in mammals since its deletion abolishes 24-hour activity patterning, an important physiological output of the clockwork. However, whether or not Bmal1-/- mice can nevertheless display molecular 24-hour rhythms is unknown. Here, we determined whether Bmal1 function is necessary for daily molecular oscillations in two tissues – skin fibroblasts and liver. Unexpectedly, both tissues exhibited robust 24-hour oscillations over 2-3 days in the absence of any exogenous synchronizers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in Bmal1 knockouts. Indeed, molecular oscillations were pervasive throughout the transcriptome, proteome and phosphoproteome of Bmal1-/- mice. In particular, several proteins exhibited rhythmic phosphorylation in both Bmal1-proficient and -deficient cells, highlighting an unanticipated role for post-translational regulators in 24-hour rhythms in the absence of any known clock mechanisms.
2020-02-17 | PXD009243 | Pride
Project description:U2OS cells harbor a circadian clock but express only a few rhythmic genes in constant conditions. We identified 3040 binding sites of the circadian regulators BMAL1, CLOCK and CRY1 in the U2OS genome. Most binding sites even in promoters do not correlate with detectable rhythmic transcript levels. Luciferase fusions reveal that the circadian clock supports robust but low amplitude transcription rhythms of representative promoters. However, rhythmic transcription of these potentially clock-controlled genes is masked by non-circadian transcription that overwrites the weaker contribution of the clock in constant conditions. Our data suggest that U2OS cells harbor an intrinsically rather weak circadian oscillator. The oscillator has the potential to regulate a large number of genes. The contribution of circadian versus non-circadian transcription is dependent on the metabolic state of the cell and may determine the apparent complexity of the circadian transcriptome. Analysis of temporal expression profiles of 5708 expressed genes in synchronized U2OS cells. A 60k customized microarray was designed for 6356 genes, which corresponds to roughly one fourth of the human genome. 1373 genes were assigned to circadian regulator binding sites (CRBSs), 1503 genes were specifically selected in addition to a set of 3480 random genes. For each gene 10 independent probes in two microarray replicates were performed to increase reliability of the data.
2014-05-23 | E-GEOD-57891 | biostudies-arrayexpress
Project description:U2OS cells harbor a circadian clock but express only a few rhythmic genes in constant conditions. We identified 3040 binding sites of the circadian regulators BMAL1, CLOCK and CRY1 in the U2OS genome. Most binding sites even in promoters do not correlate with detectable rhythmic transcript levels. Luciferase fusions reveal that the circadian clock supports robust but low amplitude transcription rhythms of representative promoters. However, rhythmic transcription of these potentially clock-controlled genes is masked by non-circadian transcription that overwrites the weaker contribution of the clock in constant conditions. Our data suggest that U2OS cells harbor an intrinsically rather weak circadian oscillator. The oscillator has the potential to regulate a large number of genes. The contribution of circadian versus non-circadian transcription is dependent on the metabolic state of the cell and may determine the apparent complexity of the circadian transcriptome. Analysis of temporal expression profiles of 5708 expressed genes in synchronized U2OS cells.
2014-05-23 | GSE57891 | GEO
Project description:Chromatin organization plays a crucial role in gene regulation by controlling the accessibility of DNA to transcription machinery. While significant progress has been made in understanding the regulatory role of clock proteins in circadian rhythms, how chromatin organization affects circadian rhythms remains poorly understood. Here, we employed ATAC-seq (Assay for Transposase-Accessible Chromatin with Sequencing) on FAC-sorted Drosophila clock neurons to assess genome-wide chromatin accessibility at dawn and dusk over the circadian cycle. We observed significant oscillations in chromatin accessibility at promoter and enhancer regions of hundreds of genes, with enhanced accessibility either at dusk or dawn, which correlated with their peak transcriptional activity. Notably, genes with enhanced accessibility at dusk were enriched with E-box motifs, while those more accessible at dawn were enriched with VRI/PDP1-box motifs, indicating that they are regulated by the core circadian feedback loops, PER/CLK and VRI/PDP1, respectively. Further, we observed a complete loss of chromatin accessibility rhythms in per01 null mutants, with chromatin consistently accessible at both dawn and dusk, underscoring the critical role of Period protein in driving chromatin compaction during the repression phase at dawn. Together, this study demonstrates the significant role of chromatin organization in circadian regulation, revealing how the interplay between clock proteins and chromatin structure orchestrates the precise timing of biological processes throughout the day. This work further implies that variations in chromatin accessibility might play a central role in the generation of diverse circadian gene expression patterns in clock neurons.
2024-03-05 | GSE256533 | GEO
Project description:Ketone bodies, intermediates in energy metabolism and signaling, have attracted significant attention due to their role in health and disease. We performed around the clock study on ketone bodies and ketogenesis with mice on different diets. We found that caloric restriction, a dietary intervention that improves metabolism and longevity, induced high amplitude circadian rhythms in blood βOHB. The blood βOHB rhythms resulted from rhythmic ketogenesis in the liver controlled by the interaction between the circadian clock and PPAR transcriptional networks. This interaction results in transcriptional reprogramming of in beta-oxidation and ketogenesis enzymes. The reprogramming is impaired in circadian clock mutant mice. The circadian clock gated ketogenesis contributes to the diet impact on health and longevity.
2022-08-31 | GSE211975 | GEO
Project description:In the chronobiology field, a fundamental dichotomy exists to explain daily rhythmicity of biological processes: these can be elicited in response to cyclic extrinsic/environmental signals such as light, or driven endogenously by the circadian clock. In mammals, the circadian clock ticks in almost every cell of the body, and functions based on a network of transcription-translation feedback loops. The PI3K-AKT signaling pathway relays environmental information of nutritional/metabolic state to regulate cell size and proliferation. AKT, a Serine/Threonine protein kinase, is activated by phosphorylation, where phospho-serine 473 (pAKT) serves as a hallmark for its activation. Following activation, it proceeds to phosphorylate dozens of target proteins that convey the signal to regulate gene expression and other key cellular functions. Overall, this pathway is widely known to be activated in response to feeding related signals, and previous studies in mice found elevated pAKT levels in correspondence with food ingestion. However, it is still unknown whether this can (also) be driven through intrinsic mechanisms, such as the circadian clock. Here, we inspected daily activation of AKT both in cultured cells and animal models. Unexpectedly, we found, that neither environmental cues nor the circadian clock were necessary for pAKT rhythms, which exhibited ultradian, rather than circadian, cycles of phosphorylation. In addition, hepatic gene expression also exhibited short rhythms in clock disrupted mice, corresponding with AKT related genes/functions. Reciprocally, inhibition of AKT phosphorylation did not affect the rhythmicity of the circadian clock. Overall, our findings uncover temporal regulation of AKT activation and reveal ultradian molecular rhythmicity that cycles independently of the canonical circadian clock.
2021-11-28 | GSE171975 | GEO
Project description:Recent evidence suggest that the circadian timing system plays an important role in the control of renal function and maintaining blood pressure. Here, we analyzed circadian rhythms of urinary excretion of sodium and potassium in wild-type mice and mice lacking circadian transcriptional activator clock. Analysis of urines collected at hourly intervals over a 24-hour period revealed dramatic changes in rhythms of sodium and potassium excretion in clock(-/-) mice. In parallel, significant differences in circadian pattern of plasma aldosterone levels, but not in the 24-hour mean aldosterone levels, were observed. Microarray-based profiling of renal transcriptomes demonstrated that clock(-/-) mice exhibit dysregulation in multiple mechanisms involved in maintaining sodium and potassium balance by the kidney. The most significant changes were detected in the expression levels of several key enzymes (Cyp4a14, Cyp4a12a and Cyp4a12b) required for the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a powerful regulator of renal sodium and potassium excretion, renal vascular tone and blood pressure. The 20-HETE levels measured in kidney microsomes of wild-type mice followed a circadian-like temporal pattern. In clock(-/-) mice, the acrophase of this rhythm was shifted by 8 hours and the 24-hour mean levels of 20-HETE were significantly decreased. These results demonstrate that circadian rhythms of urine electrolyte excretion are largely dependent on the circadian clock activity and indicate that circadian oscillations in renal 20-HETE content could be an important mechanism of blood pressure regulation. We examined the temporal profiles of gene expression in mouse whole kidney. Animals were sacrificed for microdissection every 4 hours, i.e. at ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20 (ZT M-bM-^@M-^S Zeitgeber (circadian) time, indicates time of light-on as ZT0 and time of light-off as ZT12). The microarray hybridization was performed in duplicates on pools of RNA composed of equivalent amounts of RNA prepared from teo or three animals at each ZT time-point.
2012-04-29 | E-GEOD-27366 | biostudies-arrayexpress
Project description:Recent evidence suggest that the circadian timing system plays an important role in the control of renal function and maintaining blood pressure. Here, we analyzed circadian rhythms of urinary excretion of sodium and potassium in wild-type mice and mice lacking circadian transcriptional activator clock. Analysis of urines collected at hourly intervals over a 24-hour period revealed dramatic changes in rhythms of sodium and potassium excretion in clock(-/-) mice. In parallel, significant differences in circadian pattern of plasma aldosterone levels, but not in the 24-hour mean aldosterone levels, were observed. Microarray-based profiling of renal transcriptomes demonstrated that clock(-/-) mice exhibit dysregulation in multiple mechanisms involved in maintaining sodium and potassium balance by the kidney. The most significant changes were detected in the expression levels of several key enzymes (Cyp4a14, Cyp4a12a and Cyp4a12b) required for the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a powerful regulator of renal sodium and potassium excretion, renal vascular tone and blood pressure. The 20-HETE levels measured in kidney microsomes of wild-type mice followed a circadian-like temporal pattern. In clock(-/-) mice, the acrophase of this rhythm was shifted by 8 hours and the 24-hour mean levels of 20-HETE were significantly decreased. These results demonstrate that circadian rhythms of urine electrolyte excretion are largely dependent on the circadian clock activity and indicate that circadian oscillations in renal 20-HETE content could be an important mechanism of blood pressure regulation.
2012-04-30 | GSE27366 | GEO