Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA300419 | ENA |
REPOSITORIES: ENA
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Project description:The circadian clock is a ubiquitous timekeeping system that organizes the behavior and physiology of organisms over the day and night. The clockwork orchestrates a multitude of metabolic processes as illustrated by previous global transcriptomics and proteomics studies, and the existence of daily rhythms of reduction and oxidation (redox) in a range of diverse species. However, the reciprocal question of whether metabolism can alter the clockwork remains largely unaddressed. Here we identify the pentose phosphate pathway (PPP), a critical source of cellular reducing power in the form of NADPH, as an important modulator of circadian oscillations. We show that genetic and pharmacologic inhibition of the PPP perturbs circadian gene expression and metabolic rhythms in human cells. Pharmacologic inhibition of the PPP caused similar effects in mouse tissues, and altered the pattern of rhythmic behavior in Drosophila. These manipulations also altered genome wide DNA-binding activity of the circadian transcription factors BMAL1 and CLOCK through a mechanism likely involving the redox-sensitive histone acetyltransferase p300. Thus, disruption of the PPP regulates circadian rhythms via modulation of NADPH metabolism, highlighting redox reactions as a novel connector of metabolic cycles and transcriptional oscillations in nucleated cells.
2016-08-18 | GSE74439 | GEO
Project description:Cyanobacteria are increasingly being considered for use in large-scale outdoor production of fuels and industrial chemicals. Cyanobacteria can anticipate daily changes in light availability using an internal circadian clock and rapidly alter their metabolic processes in response to changes light availability. Understanding how signals from the internal circadian clock and external light availability are integrated to control metabolic shifts will be important for engineering cyanobacteria for production in natural outdoor environments. This study has assessed how “knowing” the correct time of day, via the circadian clock, affects metabolic changes when a cyanobacterium goes through a dark-to-light transition. Our data show that the circadian clock plays an important role in inhibiting activation of the oxidative pentose phosphate pathway in the morning. Synechococcus elongatus PCC 7942 is a genetically tractable model cyanobacterium that has been engineered to produce industrially relevant biomolecules and is the best-studied model for a prokaryotic circadian clock. However, the organism is commonly grown in continuous light in the laboratory, and data on metabolic processes under diurnal conditions are lacking. Moreover, the influence of the circadian clock on diurnal metabolism has been investigated only briefly. Here, we demonstrate that the circadian oscillator influences rhythms of metabolism during diurnal growth, even though light–dark cycles can drive metabolic rhythms independently. Moreover, the phenotype associated with loss of the core oscillator protein, KaiC, is distinct from that caused by absence of the circadian output transcriptional regulator, RpaA (regulator of phycobilisome-associated A). Although RpaA activity is important for carbon degradation at night, KaiC is dispensable for those processes. Untargeted metabolomics analysis and glycogen kinetics suggest that functional KaiC is important for metabolite partitioning in the morning. Additionally, output from the oscillator functions to inhibit RpaA activity in the morning, and kaiC-null strains expressing a mutant KaiC phosphomimetic, KaiC-pST, in which the oscillator is locked in the most active output state, phenocopies a ΔrpaA strain. Inhibition of RpaA by the oscillator in the morning suppresses metabolic processes that normally are active at night, and kaiC-null strains show indications of oxidative pentose phosphate pathway activation as well as increased abundance of primary metabolites. Inhibitory clock output may serve to allow secondary metabolite biosynthesis in the morning, and some metabolites resulting from these processes may feed back to reinforce clock timing.
2016-04-28 | ST000395 | MetabolomicsWorkbench
Project description:Cyanobacteria are increasingly being considered for use in large-scale outdoor production of fuels and industrial chemicals. Cyanobacteria can anticipate daily changes in light availability using an internal circadian clock and rapidly alter their metabolic processes in response to changes light availability. Understanding how signals from the internal circadian clock and external light availability are integrated to control metabolic shifts will be important for engineering cyanobacteria for production in natural outdoor environments. This study has assessed how “knowing” the correct time of day, via the circadian clock, affects metabolic changes when a cyanobacterium goes through a dark-to-light transition. Our data show that the circadian clock plays an important role in inhibiting activation of the oxidative pentose phosphate pathway in the morning. Synechococcus elongatus PCC 7942 is a genetically tractable model cyanobacterium that has been engineered to produce industrially relevant biomolecules and is the best-studied model for a prokaryotic circadian clock. However, the organism is commonly grown in continuous light in the laboratory, and data on metabolic processes under diurnal conditions are lacking. Moreover, the influence of the circadian clock on diurnal metabolism has been investigated only briefly. Here, we demonstrate that the circadian oscillator influences rhythms of metabolism during diurnal growth, even though light–dark cycles can drive metabolic rhythms independently. Moreover, the phenotype associated with loss of the core oscillator protein, KaiC, is distinct from that caused by absence of the circadian output transcriptional regulator, RpaA (regulator of phycobilisome-associated A). Although RpaA activity is important for carbon degradation at night, KaiC is dispensable for those processes. Untargeted metabolomics analysis and glycogen kinetics suggest that functional KaiC is important for metabolite partitioning in the morning. Additionally, output from the oscillator functions to inhibit RpaA activity in the morning, and kaiC-null strains expressing a mutant KaiC phosphomimetic, KaiC-pST, in which the oscillator is locked in the most active output state, phenocopies a ΔrpaA strain. Inhibition of RpaA by the oscillator in the morning suppresses metabolic processes that normally are active at night, and kaiC-null strains show indications of oxidative pentose phosphate pathway activation as well as increased abundance of primary metabolites. Inhibitory clock output may serve to allow secondary metabolite biosynthesis in the morning, and some metabolites resulting from these processes may feed back to reinforce clock timing.
2016-05-04 | ST000394 | MetabolomicsWorkbench
Project description:Circadian biology regulates inflammatory responses in mice via the clock protein REVERBα, resulting in altered mortality and morbidity. The influence of this immune-modulation pathway in humans is unclear, but may affect outcomes after transplant. We sought to determine whether the circadian clock affects primary graft dysfunction after lung transplantation, and the role of the clock protein REVERBα. In this study we investigated the action of a synthetic REVERB ligand, (GSK4112) in human monocyte-derived macrophages.
2019-05-13 | E-MTAB-6478 | biostudies-arrayexpress
Project description:The circadian clock controls many aspects of physiology, but it remains undescribed whether extracellular vesicles (including exosomes) involved in cell-cell communications between tissues are regulated in a circadian pattern. We demonstrate a 24 h rhythmic abundance of individual proteins in exosomes using liquid chromatography-mass spectrometry in circadian-synchronised tendon fibroblasts. Further, the release of exosomes enriched in RNA-binding proteins was temporally separated from those enriched in cytoskeletal and matrix proteins, which peaked during the end of the light phase. Finally, we targeted the protein sorting mechanism in the exosome biogenesis pathway and established (by knockdown of circadian-regulated flotillin-1) that matrix metalloproteinase 14 abundance in tendon fibroblast exosomes is under flotillin-1 regulation. In conclusion, we have identified proteomic time signatures for exosomes released by tendon fibroblasts which supports the view that the circadian clock regulates protein cargo in exosomes involved in cell-cell crosstalk.
2022-05-19 | PXD022393 | Pride
Project description: Not available
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:The plant circadian clock exerts a critical role in the regulation of multiple biological processes including responses to biotic and abiotic stresses. It is estimated that the clock regulates up to 80% of the transcriptome in Arabidopsis, thus understanding the molecular mechanisms that control this rhythmic transcriptome requires identification of the targets of each clock component. The Arabidopsis core clock is partially comprised of a transcriptional regulatory loop between the MYB domain containing transcription factors CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY), and TIMING OF CAB EXPRESSION1 (TOC1). As a key component of the clock, CCA1 is able to initiate and set the phase of clock-controlled rhythms. CCA1 regulates the transcription of several genes by directly binding to the evening element (EE) motif primarily found in the promoters of evening expressed genes. Using a genome-wide approach we have identified direct targets of CCA1 in plants grown in constant (LL) and driven conditions (LD). These CCA1 targets are enriched for a myriad of biological processes and stress responses. While many of these target genes are evening phased and contain the EE in their promoter regions, a significant subset is morning phased and lack an EE. Furthermore, several CCA1 targets do not cycle in either LL or LD or both. Expression analysis in CCA1 overexpressing plants confirms CCA1 regulation of analyzed targets. Our results emphasize an expanded role for the circadian clock in regulation of key pathways in Arabidopsis, and provide a comprehensive and solid resource for future functional studies. ChIP-Seq of CCA1-GFP plants under control of the CCA1 promoter in continuous light and diel conditions
2015-07-26 | E-GEOD-70533 | biostudies-arrayexpress
Project description:Systematic identification of regulators of oxidative stress reveals non-canonical roles for peroxisomal import and the pentose phosphate pathway
| PRJNA594165 | ENA
Project description: Not available
| S-EPMC4686780 | biostudies-literature