scholarly journals Machine Learning Helps Identify CHRONO as a Circadian Clock Component

PLoS Biology ◽  
2014 ◽  
Vol 12 (4) ◽  
pp. e1001840 ◽  
Author(s):  
Ron C. Anafi ◽  
Yool Lee ◽  
Trey K. Sato ◽  
Anand Venkataraman ◽  
Chidambaram Ramanathan ◽  
...  
2019 ◽  
Vol 116 (11) ◽  
pp. 5102-5107 ◽  
Author(s):  
Percy Griffin ◽  
Julie M. Dimitry ◽  
Patrick W. Sheehan ◽  
Brian V. Lananna ◽  
Chun Guo ◽  
...  

Circadian dysfunction is a common attribute of many neurodegenerative diseases, most of which are associated with neuroinflammation. Circadian rhythm dysfunction has been associated with inflammation in the periphery, but the role of the core clock in neuroinflammation remains poorly understood. Here we demonstrate that Rev-erbα, a nuclear receptor and circadian clock component, is a mediator of microglial activation and neuroinflammation. We observed time-of-day oscillation in microglial immunoreactivity in the hippocampus, which was disrupted in Rev-erbα−/− mice. Rev-erbα deletion caused spontaneous microglial activation in the hippocampus and increased expression of proinflammatory transcripts, as well as secondary astrogliosis. Transcriptomic analysis of hippocampus from Rev-erbα−/− mice revealed a predominant inflammatory phenotype and suggested dysregulated NF-κB signaling. Primary Rev-erbα−/− microglia exhibited proinflammatory phenotypes and increased basal NF-κB activation. Chromatin immunoprecipitation revealed that Rev-erbα physically interacts with the promoter regions of several NF-κB–related genes in primary microglia. Loss of Rev-erbα in primary astrocytes had no effect on basal activation but did potentiate the inflammatory response to lipopolysaccharide (LPS). In vivo, Rev-erbα−/− mice exhibited enhanced hippocampal neuroinflammatory responses to peripheral LPS injection, while pharmacologic activation of Rev-erbs with the small molecule agonist SR9009 suppressed LPS-induced hippocampal neuroinflammation. Rev-erbα deletion influenced neuronal health, as conditioned media from Rev-erbα–deficient primary glial cultures exacerbated oxidative damage in cultured neurons. Rev-erbα−/− mice also exhibited significantly altered cortical resting-state functional connectivity, similar to that observed in neurodegenerative models. Our results reveal Rev-erbα as a pharmacologically accessible link between the circadian clock and neuroinflammation.


2018 ◽  
Vol 220 (3) ◽  
pp. 661-663 ◽  
Author(s):  
Fiona E. Belbin ◽  
Antony N. Dodd

2020 ◽  
Author(s):  
Zihao Zhu ◽  
Marcel Quint ◽  
Muhammad Usman Anwer

SummaryPredictable changes in light and temperature during a diurnal cycle are major entrainment cues that enable the circadian clock to generate internal biological rhythms that are synchronized with the external environment. With the average global temperature predicted to keep increasing, the intricate light-temperature coordination that is necessary for clock functionality is expected to be seriously affected. Hence, understanding how temperature signals are perceived by the circadian clock has become an important issue, especially in light of climate change scenarios. In Arabidopsis, the clock component EARLY FLOWERING 3 (ELF3) not only serves as an essential light Zeitnehmer, but also functions as a thermosensor participating in thermomorphogenesis. However, the role of ELF3 in temperature entrainment of the circadian clock is not fully understood. Here, we report that ELF3 is essential for delivering temperature input to the clock. We demonstrate that in the absence of ELF3, the oscillator was unable to properly respond to temperature changes, resulting in an impaired gating of thermoresponses. Consequently, clock-controlled physiological processes such as rhythmic growth and cotyledon movement were disturbed. Together, our results reveal that ELF3 is an essential Zeitnehmer for temperature sensing of the oscillator, and thereby for coordinating the rhythmic control of thermoresponsive physiological outputs.


2019 ◽  
Vol 116 (21) ◽  
pp. 10435-10440 ◽  
Author(s):  
Mokryun Baek ◽  
Stela Virgilio ◽  
Teresa M. Lamb ◽  
Oneida Ibarra ◽  
Juvana Moreira Andrade ◽  
...  

Circadian clocks generate rhythms in cellular functions, including metabolism, to align biological processes with the 24-hour environment. Disruption of this alignment by shift work alters glucose homeostasis. Glucose homeostasis depends on signaling and allosteric control; however, the molecular mechanisms linking the clock to glucose homeostasis remain largely unknown. We investigated the molecular links between the clock and glycogen metabolism, a conserved glucose homeostatic process, inNeurospora crassa. We find that glycogen synthase (gsn) mRNA, glycogen phosphorylase (gpn) mRNA, and glycogen levels, accumulate with a daily rhythm controlled by the circadian clock. Because the synthase and phosphorylase are critical to homeostasis, their roles in generating glycogen rhythms were investigated. We demonstrate that whilegsnwas necessary for glycogen production, constitutivegsnexpression resulted in high and arrhythmic glycogen levels, and deletion ofgpnabolishedgsnmRNA rhythms and rhythmic glycogen accumulation. Furthermore, we show thatgsnpromoter activity is rhythmic and is directly controlled by core clock component white collar complex (WCC). We also discovered that WCC-regulated transcription factors, VOS-1 and CSP-1, modulate the phase and amplitude of rhythmicgsnmRNA, and these changes are similarly reflected in glycogen oscillations. Together, these data indicate the importance of clock-regulatedgsntranscription over signaling or allosteric control of glycogen rhythms, a mechanism that is potentially conserved in mammals and critical to metabolic homeostasis.


2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Tiffany Liu ◽  
Jenny Carlsson ◽  
Tomomi Takeuchi ◽  
Linsey Newton ◽  
Eva M. Farré

2019 ◽  
Vol 116 (43) ◽  
pp. 21893-21899 ◽  
Author(s):  
Maria A. Nohales ◽  
Steve A. Kay

Circadian clock circuitry intersects with a plethora of signaling pathways to adequately time physiological processes to occur at the most appropriate time of the day and year. However, our mechanistic understanding of how the clockwork is wired to its output is limited. Here we uncover mechanistic connections between the core clock component GIGANTEA (GI) and hormone signaling through the modulation of key components of the transduction pathways. Specifically, we show how GI modulates gibberellin (GA) signaling through the stabilization of the DELLA proteins, which act as negative components in the signaling of this hormone. GI function within the GA pathway is required to precisely time the permissive gating of GA sensitivity, thereby determining the phase of GA-regulated physiological outputs.


2015 ◽  
Vol 112 (33) ◽  
pp. 10479-10484 ◽  
Author(s):  
Xue Liang ◽  
Frederic D. Bushman ◽  
Garret A. FitzGerald

In mammals, multiple physiological, metabolic, and behavioral processes are subject to circadian rhythms, adapting to changing light in the environment. Here we analyzed circadian rhythms in the fecal microbiota of mice using deep sequencing, and found that the absolute amount of fecal bacteria and the abundance of Bacteroidetes exhibited circadian rhythmicity, which was more pronounced in female mice. Disruption of the host circadian clock by deletion of Bmal1, a gene encoding a core molecular clock component, abolished rhythmicity in the fecal microbiota composition in both genders. Bmal1 deletion also induced alterations in bacterial abundances in feces, with differential effects based on sex. Thus, although host behavior, such as time of feeding, is of recognized importance, here we show that sex interacts with the host circadian clock, and they collectively shape the circadian rhythmicity and composition of the fecal microbiota in mice.


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