Experimental and Computational Insights into the Mechanism that CHRONO Regulates the Circadian Clock
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA996619 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The pace of the endogenous circadian clock is important for organisms to maintain homeostasis. CHRONO has been shown to play an important role in regulating the period of the mammalian clock and has recently been implicated to function in several important physiological aspects. To function properly, CHRONO needs to enter the nucleus to repress transcription. However, how CHRONO enters the nucleus and regulates the circadian clock remains unknown. Here, we report the nuclear localization signal of CHRONO and the genome-scale cistrome of CHRONO. We show that CHRONO acts as a transcriptional repressor on Jun/Fos complexes in addition to the classical BMAL1/CLOCK complexes. We further developed a mathematical model and the model simulations strongly agreed with our findings that CHRONO acts on both REV-ERBα and BMAL1 to regulate the circadian period. The model also sheds light on the fact that CHRONO cycles in most of the mammalian tissues. Thus, our experimental and computational approaches reveal the molecular mechanisms of an important circadian component, CHRONO.
2025-02-11 | GSE237793 | GEO
Project description:The pace of the endogenous circadian clock is important for organisms to maintain homeostasis. CHRONO has been shown to play an important role in regulating the period of the mammalian clock and has recently been implicated to function in several important physiological aspects. To function properly, CHRONO needs to enter the nucleus to repress transcription. However, how CHRONO enters the nucleus and regulates the circadian clock remains unknown. Here, we report the nuclear localization signal of CHRONO and the genome-scale cistrome of CHRONO. We show that CHRONO acts as a transcriptional repressor on Jun/Fos complexes in addition to the classical BMAL1/CLOCK complexes. We further developed a mathematical model and the model simulations strongly agreed with our findings that CHRONO acts on both REV-ERBα and BMAL1 to regulate the circadian period. The model also sheds light on the fact that CHRONO cycles in most of the mammalian tissues. Thus, our experimental and computational approaches reveal the molecular mechanisms of an important circadian component, CHRONO.
2025-02-11 | GSE247830 | GEO
Project description:Experimental and Computational Insights into the Mechanism that CHRONO Regulates the Circadian Clock
| PRJNA1040794 | ENA
Project description:Peripheral nervous system injuries lead to long-term neurological disability due to limited axonal regenerative ability. Injury-dependent and more recently injury-independent physiological mechanisms have provided important molecular insight into regenerative mechanisms. However, whether common molecular denominators underpinning both injury-dependent and independent biological processes exist remains unclear. We initially performed a comparative analysis of recently generated transcriptomic datasets associated with the regenerative ability of sciatic dorsal root ganglia (DRG). Surprisingly, circadian rhythms were identified as a the most significantly enriched biological process associated with regenerative capability. We demonstrate that DRG neurons possess an endogenous circadian clock with a 24h oscillations of circadian genes and that their regenerative ability displays a diurnal oscillation in a mouse model of sciatic nerve injury. Consistently, transcriptomic analysis of DRG neurons showed a significant time-of-day dependent enrichment for processes associated with neuronal development and axonal growth, for regeneration and circadian associated genes, including the core clock genes Bmal1 and Clock. Indeed, DRG-specific ablation of the non-redundant clock gene Bmal1showed that it is required for regenerative gene expression, neuronal intrinsic circadian axonal regeneration and target reinnervation. Lastly, Lithium, a chrono-active compound, enhanced nerve regeneration, in wildtype but not in clock genes Bmal1 and Cry1/2-deficient mice. Together, these data demonstrate that daily rhythms and the circadian clock fine-tune the regenerative response of DRG neurons, and they advocate for the use of chrono-active strategies in time-day dependent modulation of nerve repair.
2024-01-19 | GSE235687 | GEO
Project description:The circadian system plays an essential role in regulating timing of body metabolism in humans. Indeed, circadian misalignments are strongly associated with high rates of metabolic disorders. Molecular makeup of the circadian oscillator can be deciphered in cells cultured in vitro, and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo.
We aimed at assessing molecular clock properties in dermal fibroblasts established from the skin biopsies of seventeen Type 2 diabetic obese and non-obese patients and eleven healthy controls. Following in vitro synchronization, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters.
We observed a strong inverse correlation between HbA1c values and circadian period length within cells from the Type 2 diabetic group. RNA sequencing analysis conducted in this group samples revealed that ICAM1 encoding for the endothelial adhesion protein was differentially expressed between Type 2 diabetic compensated and non-compensated fibroblasts, and correlated with the period length. Furthermore, ICAM1 expression is driven by rhythmic CLOCK binding.
We provide for the first time a potential molecular link between severity of Type 2 diabetes and circadian clock machinery, which paves a way for further mechanistic understanding of circadian oscillator changes upon Type 2 diabetes in humans.
| EGAS00001003622 | EGA
Project description:The circadian clock is comprised of proteins that form negative feedback loops, which regulate the timing of global gene expression in a coordinated 24 hour cycle. As a result, the plant circadian clock is responsible for regulating numerous physiological processes central to growth and survival. To date, most plant circadian clock studies have relied on diurnal transcriptome changes to elucidate molecular connections between the circadian clock and observable phenotypes in wild-type plants. Here, we have combined high-throughput RNA-sequencing and mass spectrometry to comparatively characterize the lhycca1, prr7prr9, gi and toc1 circadian clock mutant rosette transcriptome and proteome at the end-of-day and end-of-night.
2018-01-02 | PXD004763 | Pride
Project description:Circadian rhythms are a series of endogenous autonomous 24-hour oscillations generated by the circadian clock. At the molecular level, the circadian clock is generated by a transcription-translation feedback loop, where BMAL1 and CLOCK transcription factors of the positive arm activate the expression of CRYPTOCHROME and PERIOD (PER) genes of the negative arm as well as the circadian clock-regulated genes. In this project, we aimed at finding the interactome of PER2 protein in human U2OS osteosarcoma cell line using proximity-dependent biotin identification (BioID) technique. U2OS clones overexpressing PER2-BioID2 or BioID2 were treated with dexamethasone in order to reset the circadian rhythm, and cells were then incubated in biotin-containing media for 12 hours to label the proteins in close proximity of PER2-BioID2. Samples were collected after 36 and 48 hours of the resetting to identify the labeled proteins by mass spectrometry. In addition to known interactors such as CRY1 and CRY2, many novel interactors were identified. In summary, we obtained a network of PER2 interactome and confirmed some of the novel interactions using classical the co-immunoprecipitation method.
2022-04-22 | PXD025179 | Pride
Project description:Circadian desynchrony induced by shiftwork or jetlag is detrimental to metabolic health, but how synchronous or desynchronous signals are transmitted among tissues is unknown. We report that liver molecular clock dysfunction is signaled to the brain through the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chrono-disruption.
2024-12-18 | GSE248462 | GEO
Project description:Influence of diet and neuronal clk (clock) activity on hemolymph proteomics. We have shown that as photoreceptors die (in the fly) they necrose, which results in their intercellular contents leaking into the hemolymph. We hypothesize that this process is regulated by diet and circadian clock control.
Analysis of differential protein expression in the hemolymph from flies reared on a high protein diet. Comparison of flies with and without a functional circadian clock within their photoreceptors.
Species/Strain: Drosophila, Elav-GeneSwitch-GAL4>UAS-Clk-DN1 (+/- RU486), female
2021-01-30 | MSV000086781 | MassIVE
Project description:Circadian clocks drive ~24 hr rhythms in tissue physiology. They rely on transcriptional/translational feedback loops driven by interacting networks of clock complexes.To gain insights into the role of the mammary clock, circadian time-series microarrays were performed to identify rhythmic genes in vivo. Breast tissues were isolated at 4 hr intervals for two circadian (24 hourly) cycles, from mice kept under constant darkness to avoid any light- or dark-driven genes.
2017-12-01 | E-MTAB-5330 | biostudies-arrayexpress