Mus musculus
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ABSTRACT:
PROVIDER: PRJNA143375 | ENA |
REPOSITORIES: ENA
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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:Circadian rhythms synchronize cellular activities with the Earth’s 24-hour cycle, primarily regulated by clock genes that influence metabolism, physiology, and osteogenesis. While genetic regulation of circadian rhythms is well characterized, how extracellular mechanical forces modulate these rhythms during iPSC osteogenic differentiation remains unclear. Here, we show that shaking culture, which promotes three-dimensional iPSC-EB formation, disrupts clock gene oscillations by activating YAP-TEAD signaling. Inhibition of YAP-TEAD with verteporfin restores circadian oscillations and enhances osteogenesis, highlighting a biomechanical-circadian interplay with implications for regenerative medicine.
2025-03-14 | GSE291628 | GEO
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 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.
2012-06-01 | GSE30411 | GEO
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: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 role of circadian clocks in regulating metabolic processes has been studied extensively. Yet, the physiological impacts of the circadian system on metabolic states across species and life stages remain to be explored. This study investigates the relationship between circadian rhythms and metabolic regulation in the fat body of Drosophila larva, an organ crucial for maintaining metabolic homeostasis, growth and developmental timing. Larval fat body is analogous to the mammalian liver and adipose tissue but lacks a canonical circadian clock. Around-the-clock RNA-sequencing analysis on the fat bodies of wild-type and period clock gene null mutant larvae revealed circadian rhythms in the transcriptome of wild-type larvae. Surprisingly, period mutant exhibited 12-h rhythms in the expression of numerous genes, particularly those involved in peroxisome function, lipid metabolism, and oxidative stress response. Consistent with these transcriptomic data, peroxisome biogenesis and activity demonstrated 12-h rhythms in period mutant fat bodies. Furthermore, levels of reactive oxygen species displayed inverse-phased rhythms to that of lipid peroxidation, with 24-h rhythms in wild-type and 12-h rhythms in period mutant fat bodies. Moreover, while daily fat storage levels in wild-type larvae remained constant, period mutants exhibited fluctuations with a 12-h period and a net reduction in body fat storage. Collectively, our results identified a clock-independent ultradian rhythms in lipid metabolism, which may contribute to maintaining the metabolic, energetic, and redox homeostasis essential for larval survival and development.
2024-12-19 | GSE282559 | GEO
Project description:Eukaryotic circadian clocks include transcriptional/translational feedback loops that drive 24-hour rhythms of transcription.These transcriptional rhythms underlie oscillations of protein abundance, thereby mediating circadian rhythms of behavior, physiology, and metabolism. Numerous studies over the last decade have employed microarrays to profile circadian transcriptional rhythms in various organisms and tissues. Here we use RNA sequencing (RNA-Seq) to profile the circadian transcriptome of *Drosophila melanogaster* brain from wild-type and *period*-null clock-defective animals. We identify several hundred transcripts whose abundance oscillates with 24-hour periods, including a number of non-coding RNAs (ncRNAs) that were not identified in previous microarray studies. Of particular interest are *U snoRNA host genes* (*Uhgs*), a family of cycling ncRNAs that encode the precursors of over 50 box C/D snoRNAs, key regulators of ribosomal biogenesis. Transcriptional profiling at the level of individual exons reveals alternative splice isoforms for many genes whose relative abundances are regulated by either *period* or circadian time, although the effect of circadian time is muted in comparison to that of *period*. Interestingly, *period* loss-of-function significantly alters the frequency of RNA editing at a number of editing sites, suggesting an unexpected link between a key circadian gene and RNA editing. We also identify tens of thousands of novel splicing events beyond those previously annotated by the modENCODE consortium, including several that affect key circadian genes. These studies demonstrate extensive circadian control of ncRNA expression, reveal the extent of clock control of alternative splicing and RNA editing, and provide a novel, genome-wide map of splicing in *Drosophila* brain. RNA-Seq transcriptional profiling of Drosophila brains from wildtype and period loss-of-function (per0) flies with time points taken over two days in constant darkness. Time points at CT24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, and 68. 10-12 brains per time point.
2012-03-27 | E-GEOD-36108 | biostudies-arrayexpress
Project description:Diurnal (i.e., 24-hour) physiological rhythms depend on transcriptional programs controlled by a set of circadian clock genes/proteins. Systemic factors like humoral and neuronal signals, oscillations in body temperature, and food intake align physiological circadian rhythms with external time. Thyroid hormones (THs) are major regulators of circadian clock target processes such as energy metabolism, but little is known about how fluctuations in TH levels affect the circadian coordination of tissue physiology. In this study, a high triiodothyronine (T3) state was induced in mice by supplementing T3 in the drinking water, which affected body temperature, and oxygen consumption in a time-of-day dependent manner. 24-hour transcriptome profiling of liver tissue identified 37 robustly and time independently T3 associated transcripts as potential TH state markers in the liver. Such genes participated in xenobiotic transport, lipid and xenobiotic metabolism. We also identified 10 – 15 % of the liver transcriptome as rhythmic in control and T3 groups, but only 4 % of the liver transcriptome (1,033 genes) were rhythmic across both conditions – amongst these several core clock genes. In-depth rhythm analyses showed that most changes in transcript rhythms were related to mesor (50%), followed by amplitude (10%), and phase (10%). Gene set enrichment analysis revealed TH state dependent reorganization of metabolic processes such as lipid and glucose metabolism. At high T3 levels, we observed weakening or loss of rhythmicity for transcripts associated with glucose and fatty acid metabolism, suggesting increased hepatic energy turnover. In sum, we provide evidence that tonic changes in T3 levels restructure the diurnal liver metabolic transcriptome independent of local molecular circadian clocks.
2022-07-26 | GSE199998 | GEO