Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA177601 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Circadian rhythms are responsive to a variety of external cues, light and metabolism being the most important. In mammals, the light signal is sensed by the retina and transmitted to the SCN master clock, where it is translated into the molecular oscillator via regulation of clock gene transcription. The signalling pathways governing the molecular translation from metabolic signals to circadian output in peripheral oscillators, in contrast, are less understood. FOXO transcription factors are known to translate external metabolic cues to internal transcriptional programs. In the past couple of years it has become evident that both FOXO transcription factors and the circadian clock are of key importance in the underlying mechanisms of ageing and the regulation of metabolism. We now show FOXO3 to be a crucial modulator of circadian rhythmicity via direct transcriptional regulation of Clock, a core component of the molecular oscillator, and identify FOXO3 as a novel link in the circadian feedback loop, which is required for circadian rhythms in liver. We propose that FOXO3 directly feeds back into the circadian oscillator in response to metabolic cues.
2014-06-03 | GSE41555 | GEO
Project description:Circadian rhythms are responsive to a variety of external cues, light and metabolism being the most important. In mammals, the light signal is sensed by the retina and transmitted to the SCN master clock, where it is translated into the molecular oscillator via regulation of clock gene transcription. The signalling pathways governing the molecular translation from metabolic signals to circadian output in peripheral oscillators, in contrast, are less understood. FOXO transcription factors are known to translate external metabolic cues to internal transcriptional programs. In the past couple of years it has become evident that both FOXO transcription factors and the circadian clock are of key importance in the underlying mechanisms of ageing and the regulation of metabolism. We now show FOXO3 to be a crucial modulator of circadian rhythmicity via direct transcriptional regulation of Clock, a core component of the molecular oscillator, and identify FOXO3 as a novel link in the circadian feedback loop, which is required for circadian rhythms in liver. We propose that FOXO3 directly feeds back into the circadian oscillator in response to metabolic cues.
2014-06-03 | GSE41554 | GEO
Project description:MH003A:FOXO3 in control of circadian rhythms via direct regulation of Clock. Part 1: overexpression of FoxO6
| PRJNA177600 | ENA
Project description:Circadian rhythms are responsive to a variety of external cues, light and metabolism being the most important. In mammals, the light signal is sensed by the retina and transmitted to the SCN master clock, where it is translated into the molecular oscillator via regulation of clock gene transcription. The signalling pathways governing the molecular translation from metabolic signals to circadian output in peripheral oscillators, in contrast, are less understood. FOXO transcription factors are known to translate external metabolic cues to internal transcriptional programs. In the past couple of years it has become evident that both FOXO transcription factors and the circadian clock are of key importance in the underlying mechanisms of ageing and the regulation of metabolism. We now show FOXO3 to be a crucial modulator of circadian rhythmicity via direct transcriptional regulation of Clock, a core component of the molecular oscillator, and identify FOXO3 as a novel link in the circadian feedback loop, which is required for circadian rhythms in liver. We propose that FOXO3 directly feeds back into the circadian oscillator in response to metabolic cues. We performed a microarray study on synchronized NIH 3T3 cells upon transient knock-down of FoxO3 (siO3). Cells were harvested for RNA isolation 24h (time1), 30h(time2), 36h(time3) and 42h(time4) after synchronization. Experimental samples were hybridized against a reference pool of cRNA, which was derived from unsynchronized NIH 3T3 cells. AS controlgroup a scrambled siRNA was transfected. Experiments were performed 4 times, of each sample group two samples were labeled with cy5 and co-hybridized with reference RNA labeled with cy3, and two samples were labeled and hybridized in the opposite way. Microarrays used were Mouse Whole Genome Gene Expression Microarrays V1 (Agilent Technologies, Belgium)
2014-06-03 | E-GEOD-41555 | biostudies-arrayexpress
Project description:Circadian rhythms are responsive to a variety of external cues, light and metabolism being the most important. In mammals, the light signal is sensed by the retina and transmitted to the SCN master clock, where it is translated into the molecular oscillator via regulation of clock gene transcription. The signalling pathways governing the molecular translation from metabolic signals to circadian output in peripheral oscillators, in contrast, are less understood. FOXO transcription factors are known to translate external metabolic cues to internal transcriptional programs. In the past couple of years it has become evident that both FOXO transcription factors and the circadian clock are of key importance in the underlying mechanisms of ageing and the regulation of metabolism. We now show FOXO3 to be a crucial modulator of circadian rhythmicity via direct transcriptional regulation of Clock, a core component of the molecular oscillator, and identify FOXO3 as a novel link in the circadian feedback loop, which is required for circadian rhythms in liver. We propose that FOXO3 directly feeds back into the circadian oscillator in response to metabolic cues. We performed a microarray study on synchronized NIH 3T3 cells upon transient overexpression of FoxO6 (oeO6). Cells were harvested for RNA isolation 24h (time1), 30h(time2), 36h(time3) and 42h(time4) after synchronization. Experimental samples were hybridized against a reference pool of cRNA, which was derived from unsynchronized NIH 3T3 cells. Experiments were performed 4 times, of each sample group two samples were labeled with cy5 and co-hybridized with reference RNA labeled with cy3, and two samples were labeled and hybridized in the opposite way. Microarrays used were Mouse Whole Genome Gene Expression Microarrays V1 (Agilent Technologies, Belgium)
2014-06-03 | E-GEOD-41554 | biostudies-arrayexpress
Project description:The circadian clock is intricately connected with metabolism, however the precise details of these connections are incomplete. Here we used high temporal resolution metabolite profiling to determine circadian regulation of mouse liver and cell autonomous metabolism. In mouse liver, we found ~50% of metabolites were circadian, with strong enrichment of the nucleotide, amino acid, and methylation pathways. In U2OS cells, 27% of metabolites were circadian, including amino acids and NAD biosynthesis, also clock controlled in liver. To assess whether cell autonomous metabolite rhythms were clock-dependent, we used RNAi to perturb Bmal1, Cry1, and Cry2. Bmal1 knockdown eliminated most metabolite rhythms, while Cry1 generally shortened and Cry2 lengthened rhythms. Surprisingly, we found Cry1 knockdown induced 8 hr rhythms in amino acid, methylation, and vitamin metabolites, decoupling metabolite and transcriptional rhythms. These results provide the first comprehensive views of circadian liver and cell autonomous metabolism.
2017-04-05 | MTBLS292 | MetaboLights
Project description:Study on differential gene expression and splicing between wildtype and clock mutants. This study is part of a comparative analysis of the role of Protein Methyltransferase 5 in the regulation of transcriptional and post-transcriptional processes simultaneously in Arabidopsis and Drosophila. Circadian rhythms allow organisms to time biological processes to the most appropriate phases of the day/night cycle1. Post-transcriptional regulation is emerging as an important component of circadian networks2-6, but the molecular mechanisms linking the circadian clock to the control of RNA processing are largely unknown. Here we show that Protein Arginine Methyl Transferase 5 (PRMT5), which transfers methyl groups to arginine residues present in histones7 and Sm spliceosomal proteins8,9, links the circadian clock to the control of alternative splicing in plants. Mutations in prmt5impair multiple circadian rhythms in Arabidopsis thaliana and this phenotype is caused, at least in part, by a strong alteration in alternative splicing of the core-clock gene PSEUDO RESPONSE REGULATOR 9 (PRR9). Furthermore, genome wide studies show that PRMT5 contributes to regulate many pre-mRNA splicing events most likely modulating 5´splice site (5´ss) recognition. PRMT5 expression shows daily and circadian oscillations, and this contributes to mediate the circadian regulation of expression and alternative splicing of a subset of genes. Circadian rhythms in locomotor activity are also disrupted in dart5, a mutant affected in the Drosophila melanogaster PRMT5 homolog, and this is associated with alterations in splicing of the core-clock gene period (per) and several clock associated genes. Our results reveal a key role for PRMT5 in the regulation of alternative splicing and indicate that the interplay between the circadian clock and the regulation of alternative splicing by PRMT5 constitutes a common mechanism that helps organisms to synchronize physiological processes with daily changes in environmental conditions.
2010-08-24 | GSE18808 | GEO
Project description:Temporal dynamics in an organism's behavior, physiology, metabolism, and biochemistry over the course of 24 hours are governed by an inherent cellular clock. Transcriptomic studies revealed that the clock is governed by intricate transcriptional and translational feedback loops(TTFLs) involving daily transcription and translation of the clock genes. As a result, the consensus focussed on transcription as the primary driver of this daily regulation since mRNA of the clock genes show robust oscillations. However, protein dynamics across the 24-hour cycle have not been studied in great detail. The notion of mRNA rhythms corresponding to protein rhythms needs reinvestigation. Many recent studies revealed that the pattern of mRNA rhythms does not match their encoded protein rhythms. Here, we used a high-throughput quantitative mass spectrometry technique to investigate the daily variation in protein expression in a single-cell phytoplankton C.reinhardtii. We found hundreds of proteins oscillating over 24 hours. Further, we found several known and unique physiological and metabolic pathways are controlled by the circadian clock in a time-dependent manner. In addition, to gain more insights into the complex clock regulation of these pathways, we compared the RNA abundance to protein abundance. Intriguingly, we found a significant discrepancy in the peak phase distribution of RNA and proteins unraveling the intricate mechanism shaping the daily circadian physiology and metabolism in C.reinhardtii. Altogether, our study reports the first comprehensive circadian proteome and the important role of post-transcriptional control over the C.reinhardtii circadian clock.
2025-05-27 | PXD043839 | Pride
Project description:The circadian system produces ~24-hr oscillations in behavioral and physiological processes to ensure that they occur at optimal times of day and in the correct temporal order. At its core, the circadian system is composed of dedicated central clock neurons that keep time through a cell-autonomous molecular clock. To produce rhythmic behaviors, time-of-day information generated by clock neurons must be transmitted across output pathways to regulate the downstream neuronal populations that control the relevant behaviors. An understanding of the manner through which the circadian system enacts behavioral rhythms therefore requires the identification of the cells and molecules that make up the output pathways. To that end, we recently characterized the Drosophila pars intercerebralis (PI) as a major circadian output center that lies downstream of central clock neurons in a circuit controlling rest:activity rhythms. We have conducted single-cell RNA sequencing (scRNAseq) to identify potential circadian output genes expressed by PI cells, and used cell-specific RNA interference (RNAi) to knock down expression of ~40 of these candidate genes selectively within subsets of PI cells. We demonstrate that knockdown of the slowpoke (slo) potassium channel in PI cells reliably decreases circadian rest:activity rhythm strength. Interestingly, slo mutants have previously been shown to have aberrant rest:activity rhythms, in part due to a necessary function of slo within central clock cells. However, rescue of slo in all clock cells does not fully reestablish behavioral rhythms, indicating that expression in non-clock neurons is also necessary. Our results demonstrate that slo exerts its effects in multiple components of the circadian circuit, including PI output cells in addition to clock neurons, and we hypothesize that it does so by contributing to the generation of daily neuronal activity rhythms that allow for the propagation of circadian information throughout output circuits.
2020-12-01 | GSE162379 | GEO