Saccharomyces cerevisiae
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA293523 | ENA |
REPOSITORIES: ENA
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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:The 4D organization of the interphase nucleus, or the 4D Nucleome (4DN), reflects a dynamical interaction between 3D genome structure and function and its relationship to phenotype. We present initial analyses of the human 4DN, capturing genome-wide structure using chromosome conformation capture and 3D imaging, and function using RNA-sequencing. We introduce a quantitative index that measures underlying topological stability of a genomic region. Our results show that structural features of genomic regions correlate with function with surprising persistence over time. Furthermore, constructing genome-wide gene-level contact maps aided in identifying gene pairs with high potential for coregulation and colocalization in a manner consistent with expression via transcription factories. We additionally use 2D phase planes to visualize patterns in 4DN data. Finally, we evaluated gene pairs within a circadian gene module using 3D imaging, and found periodicity in the movement of clock circadian regulator and period circadian clock 2 relative to each other that followed a circadian rhythm and entrained with their expression.
2016-05-05 | GSE81087 | GEO
Project description:The circadian clock drives daily changes of physiology, including sleep-wake cycles, by regulating transcription, protein abundance and function. Circadian phosphorylation controls cellular processes in peripheral organs, but little is known about its role in brain function and synaptic activity. We applied advanced quantitative phosphoproteomics to mouse forebrain synaptoneurosomes isolated across 24h, accurately quantifying almost 8,000 phosphopeptides. Remarkably, half of the synaptic phosphoproteins, including numerous kinases, had large-amplitude rhythms peaking at rest-activity and activity-rest transitions. Bioinformatic analyses revealed global temporal control of synaptic function via phosphorylation, including synaptic transmission, cytoskeleton reorganization and excitatory/inhibitory balance. Remarkably, sleep deprivation abolished 98% of all phosphorylation cycles in synaptoneurosomes, indicating that sleep-wake cycles rather than circadian signals are main drivers of synaptic phosphorylation, responding to both sleep and wake pressures.
2019-10-14 | PXD010697 | Pride
Project description:Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. We present a computational method, dynamic motif occupancy (DynaMO), which exploits random forest modeling and clustering based enrichment analysis. DynaMO exploits TF motifs and dynamic ChIP-seq data of chromatin surrogates such as histone modifications to infer important TFs and their spatiotemporal binding in biological processes. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We further demonstrate the function of stress response regulators Msn2 and Msn4 as key TFs activating yeast glycolysis genes. Msn2/4 regulates the cellular transition from quiescence to growth by accumulating the intracellular acetyl-CoA level through glycolysis. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes.
2017-09-26 | GSE72263 | GEO
Project description:The circadian clock system coordinates metabolic, physiological, and behavioral functions across a 24-hour cycle, crucial for adapting to environmental changes. Disruptions in circadian rhythms contribute to major metabolic pathologies like obesity and Type 2 diabetes. Understanding the regulatory mechanisms governing circadian control is vital for identifying therapeutic targets. It is well characterized that chromatin remodeling at distal enhancer elements shapes the genome topology, supporting rhythmic transcriptional cycles; yet the impact of rhythmic chromatin topology and circadian enhancers in disease states is largely unexplored. In his study, we use 4C-seq techniques in mouse liver to explore how the spatial configuration of the genome adapts to diet, rewiring circadian transcription and contributing to dysfunctional metabolism. We describe daily fluctuations in chromatin contacts between distal regulatory elements of metabolic control genes in livers from lean and obese mice and identify specific lipid-responsive regions recruiting the clock molecular machinery. Our findings highlight the intricate coupling of circadian gene expression to a dynamic nuclear environment under high-fat feeding, supporting a temporally regulated program of gene expression and transcriptional adaptation to diet.
2024-08-01 | GSE254620 | GEO
Project description:<p>Circadian clocks coordinate mammalian behaviour and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.</p><p><br></p><p><strong>GC-MS assay</strong> protocols and data are reported in the current study <strong>MTBLS1286</strong>.</p><p><strong>LC-MS assay</strong> protocols and data for this study are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1285' rel='noopener noreferrer' target='_blank'><strong>MTBLS1285</strong></a>.</p>
2020-11-13 | MTBLS1286 | MetaboLights
Project description:<p>Circadian clocks coordinate mammalian behaviour and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.</p><p><br></p><p><strong>LC-MS assay</strong> protocols and data are reported in the current study <strong>MTBLS1285</strong>.</p><p><strong>GC-MS assay</strong> protocols and data for this study are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1286' rel='noopener noreferrer' target='_blank'><strong>MTBLS1286</strong></a>.</p>
2020-11-13 | MTBLS1285 | MetaboLights
Project description:Biological rhythms have important implications for human disease, as evidenced by the effects of disrupting the 24h circadian clock. While circadian rhythms are entrained to the once daily light-dark cycle of the sun, coastal marine organisms are known to exhibit 12h ultradian rhythms, corresponding to the twice daily movement of the tides. Human ancestors emerged from a circa-tidal environment millions of years ago. However, whether 12h ultradian rhythms are conserved in humans remains unknown. Here, we performed prospective, high temporal resolution transcriptome profiling in the peripheral white blood cells of three healthy subjects. Remarkably, all three subjects exhibited a shared transcriptional program demonstrating robust ~12h rhythms. Pathway analysis implicated 12h transcriptional oscillations primarily affected core cellular processes, including RNA and protein metabolism, with strong homology to the 12h gene programs previously identified in cnidarian marine species. These results establish the existence of 12h biological rhythms in humans. Such rhythms appear to have a primordial evolutionary origin dating back at least 700 million years and are likely to have far-reaching implications in human health and disease.
2023-08-07 | GSE220120 | GEO
Project description:In mammals, circadian clocks are strictly suppressed during early embryonic stages as well as pluripotent stem cells, by the lack of CLOCK/BMAL1 mediated circadian feedback loops. During ontogenesis, the innate circadian clocks emerge gradually at a late developmental stage, then, with which the circadian temporal order is invested in each cell level throughout a body. Meanwhile, in the early developmental stage, a segmented body plan is essential for an intact developmental process and somitogenesis is controlled by another cell-autonomous oscillator, the segmentation clock, in the posterior presomitic mesoderm (PSM). In the present study, focusing upon the interaction between circadian key components and the segmentation clock, we investigated the effect of the CLOCK/BMAL1 on the segmentation clock Hes7 oscillation, revealing that the expression of functional CLOCK/BMAL1 severely interferes with the ultradian rhythm of segmentation clock in induced PSM and gastruloids. RNA sequencing analysis showed that the premature expression of CLOCK/BMAL1 affects the Hes7 transcription and its regulatory pathways. These results suggest that the suppression of CLOCK/BMAL1-mediated transcriptional regulation during the somitogenesis may be inevitable for intact mammalian development.
2021-12-09 | GSE181295 | GEO