scholarly journals Genome-wide fitness assessment during diurnal growth reveals an expanded role of the cyanobacterial circadian clock protein KaiA

2018 ◽  
Author(s):  
David G. Welkie ◽  
Benjamin E. Rubin ◽  
Yong-Gang Chang ◽  
Spencer Diamond ◽  
Scott A. Rifkin ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Environmental Changes ◽  
Time Of Day ◽  
Negative Regulator ◽  
Starvation Period ◽  
Night Time ◽  
Photosynthetic Organisms ◽  
Genetic Components ◽  
Clock Protein

AbstractThe recurrent pattern of light and darkness generated by Earth’s axial rotation has profoundly influenced the evolution of organisms, selecting for both biological mechanisms that respond acutely to environmental changes and circadian clocks that program physiology in anticipation of daily variations. The necessity to integrate environmental responsiveness and circadian programming is exemplified in photosynthetic organisms such as cyanobacteria, which depend on light-driven photochemical processes. The cyanobacterium Synechococcus elongatus PCC 7942 is an excellent model system for dissecting these entwined mechanisms. Its core circadian oscillator, consisting of three proteins KaiA, KaiB, and KaiC, transmits time-of-day signals to clock-output proteins, which reciprocally regulate global transcription. Research performed under constant light facilitates analysis of intrinsic cycles separately from direct environmental responses, but does not provide insight into how these regulatory systems are integrated during light-dark cycles. Thus, we sought to identify genes that are specifically necessary in a day-night environment. We screened a dense bar-coded transposon library in both continuous light and daily cycling conditions and compared the fitness consequences of loss of each nonessential gene in the genome. Although the clock itself is not essential for viability in light-dark cycles, the most detrimental mutations revealed by the screen were those that disrupt KaiA. The screen broadened our understanding of light-dark survival in photosynthetic organisms, identified unforeseen clock-protein interaction dynamics, and reinforced the role of the clock as a negative regulator of a night-time metabolic program that is essential for S. elongatus to survive in the dark.SignificanceUnderstanding how photosynthetic bacteria respond to and anticipate natural light–dark cycles is necessary for predictive modeling, bioengineering, and elucidating metabolic strategies for diurnal growth. Here, we identify the genetic components that are important specifically under light-dark cycling conditions and determine how a properly functioning circadian clock prepares metabolism for darkness, a starvation period for photoautotrophs. This study establishes that the core circadian clock protein KaiA is necessary to enable rhythmic de-repression of a night-time circadian program.

scholarly journals Genome-wide fitness assessment during diurnal growth reveals an expanded role of the cyanobacterial circadian clock protein KaiA

2018 ◽  
Vol 115 (30) ◽  
pp. E7174-E7183 ◽  
Author(s):  
David G. Welkie ◽  
Benjamin E. Rubin ◽  
Yong-Gang Chang ◽  
Spencer Diamond ◽  
Scott A. Rifkin ◽  
...  
Keyword(s):  
Environmental Changes ◽  
Continuous Light ◽  
Axial Rotation ◽  
Time Of Day ◽  
Negative Regulator ◽  
Photosynthetic Organisms ◽  
Environmental Responsiveness ◽  
Environmental Responses ◽  
Clock Protein

The recurrent pattern of light and darkness generated by Earth’s axial rotation has profoundly influenced the evolution of organisms, selecting for both biological mechanisms that respond acutely to environmental changes and circadian clocks that program physiology in anticipation of daily variations. The necessity to integrate environmental responsiveness and circadian programming is exemplified in photosynthetic organisms such as cyanobacteria, which depend on light-driven photochemical processes. The cyanobacterium Synechococcus elongatus PCC 7942 is an excellent model system for dissecting these entwined mechanisms. Its core circadian oscillator, consisting of three proteins, KaiA, KaiB, and KaiC, transmits time-of-day signals to clock-output proteins, which reciprocally regulate global transcription. Research performed under constant light facilitates analysis of intrinsic cycles separately from direct environmental responses but does not provide insight into how these regulatory systems are integrated during light–dark cycles. Thus, we sought to identify genes that are specifically necessary in a day–night environment. We screened a dense bar-coded transposon library in both continuous light and daily cycling conditions and compared the fitness consequences of loss of each nonessential gene in the genome. Although the clock itself is not essential for viability in light–dark cycles, the most detrimental mutations revealed by the screen were those that disrupt KaiA. The screen broadened our understanding of light–dark survival in photosynthetic organisms, identified unforeseen clock–protein interaction dynamics, and reinforced the role of the clock as a negative regulator of a nighttime metabolic program that is essential for S. elongatus to survive in the dark.

scholarly journals EYES ABSENT and TIMELESS integrate photoperiodic and temperature cues to regulate seasonal physiology in Drosophila

2020 ◽  
Author(s):  
Antoine Abrieux ◽  
Yongbo Xue ◽  
Yao Cai ◽  
Kyle M. Lewald ◽  
Hoang Nhu Nguyen ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Physiological Responses ◽  
Day Length ◽  
Short Photoperiod ◽  
Eyes Absent ◽  
Winter Conditions ◽  
Clock Protein

AbstractOrganisms possess photoperiodic timing mechanisms to anticipate variations in day length and temperature as the seasons progress. The nature of the molecular mechanisms interpreting and signaling these environmental changes to elicit downstream neuroendocrine and physiological responses are just starting to emerge. Here, we demonstrate that in Drosophila melanogaster, EYES ABSENT (EYA) acts as a seasonal sensor by interpreting photoperiodic and temperature changes to trigger appropriate physiological responses. We observed that tissue-specific genetic manipulation of eya expression is sufficient to disrupt the ability of flies to sense seasonal cues, thereby altering the extent of female reproductive dormancy. Specifically we observed that EYA proteins, which peak at night in short photoperiod and accumulate at higher levels in the cold, promote reproductive dormancy in female D. melanogaster. Furthermore, we provide evidence indicating that the role of EYA in photoperiodism and temperature sensing is aided by the stabilizing action of the light-sensitive circadian clock protein TIMELESS (TIM). We postulate that increased stability and level of TIM at night under short photoperiod together with the production of cold-induced and light-insensitive TIM isoforms facilitate EYA accumulation in winter conditions. This is supported by our observations that tim null mutants exhibit reduced incidence of reproductive dormancy in simulated winter conditions, while flies overexpressing tim show an increased incidence of reproductive dormancy even in long photoperiod.Significance StatementExtracting information on calendar time from seasonal changes in photoperiod and temperature is critical for organisms to maintain circannual cycles in physiology and behavior. Here we found that in flies, EYES ABSENT (EYA) protein act as a seasonal sensor by adjusting its abundance and circadian phase in response to changes in photoperiod and temperature. We show that the manipulation of EYA levels is sufficient to impair the ability of female Drosophila to regulate seasonal variation in reproductive dormancy. Finally, our results suggest an important role of the circadian clock protein TIMELESS (TIM) in modulating EYA level through its ability to measure night length, linking the circadian clock to seasonal timing.

scholarly journals Circadian clock protein Rev-erbα regulates neuroinflammation

2019 ◽  
Vol 116 (11) ◽  
pp. 5102-5107 ◽  
Author(s):  
Percy Griffin ◽  
Julie M. Dimitry ◽  
Patrick W. Sheehan ◽  
Brian V. Lananna ◽  
Chun Guo ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Microglial Activation ◽  
Time Of Day ◽  
Resting State Functional Connectivity ◽  
Promoter Regions ◽  
Clock Component ◽  
Glial Cultures ◽  
Inflammatory Phenotype

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.

Abstract 130: Modulation of Salt and Mineralocorticoid Sensitivity of Blood Pressure by the Circadian Clock Protein Per1

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Kristen Solocinski ◽  
Xuerong Wen ◽  
Kit-Yan Cheng ◽  
Jeanette Lynch ◽  
Brian D Cain ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Circadian Clock ◽  
Clock Gene ◽  
Salt Intake ◽  
Disease Risk ◽  
Male Mice ◽  
Night Time ◽  
Increased Risk ◽  
Time Map ◽  
Clock Protein

The circadian clock is important for maintaining rhythms in physiological functions including blood pressure (BP). Circadian disruption leads to increased disease risk. The clock has also been implicated in the maintenance of a normal dip in BP at night. In humans, non-dipping (night/day difference in BP<10%) is associated with an increased risk of cardiovascular and kidney disease. Dipping status can also be affected by salt intake and by hormones such as the mineralocorticoid aldosterone. The goal of this study was to determine the effects of a high salt (HS, 4% NaCl) diet plus mineralocorticoid (deoxycorticosterone pivalate (DOCP)) on BP regulation by the circadian clock protein Per1 in C57BL/6J mice. BP was monitored in conscious, unrestrained male mice by radiotelemetry and values are reported as mean arterial pressure (MAP) ± SEM. Under control conditions, MAP in male WT mice was 112.5 ± 1.08 mmHg during the night when mice are active and decreased to 102.1 ± 1.7 mmHg during the day, a “dip” in MAP of 9.2 ± 1.3%. Similarly, Per1 KO mice dip 14 ± 1.4%, with night time MAP of 119.8 ± .9 mmHg which decreased to 103 ± 1.4 mmHg during the day. On HS/DOCP, WT mice MAP decreased from 114.5 ± 1.1 mmHg to 101.5 ± 1.92 mmHg (night indicated by shaded bars in figure). This 11.4 ± 1.9% dip in WT mice was not significantly different from what was observed under control conditions. In contrast, Per1 KO mice display a significantly attenuated dip of 5.7 ± 1.4% with night time MAP of 125.3 ± 1.5 mmHg dropping to 118.1 ± 1 mmHg during the inactive day period (p<0.05). Thus, HS/DOCP treatment in Per1 KO mice leads to non-dipping hypertension. This is the first report of this phenotype in a single clock gene KO.

scholarly journals Physiological and Genetic Bases of the Circadian Clock in Plants and Their Relationship with Herbicides Efficacy

2016 ◽  
Vol 34 (1) ◽  
pp. 191-198
Author(s):  
G. DALAZEN ◽  
A. MEROTTO JR.
Keyword(s):  
Circadian Clock ◽  
Environmental Changes ◽  
Crop Yields ◽  
Light Availability ◽  
Leaf Angle ◽  
Time Of Application ◽  
Genetic Mechanisms ◽  
Relationship Of ◽  
The Relationship

In order to adapt to daily environmental changes, especially in relation to light availability, many organisms, such as plants, developed a vital mechanism that controls time-dependent biological events: the circadian clock. The circadian clock is responsible for predicting the changes that occur in the period of approximately 24 hours, preparing the plants for the following phases of the cycle. Some of these adaptations can influence the response of weeds to the herbicide application. Thus, the objectives of this review are to describe the physiological and genetic mechanisms of the circadian clock in plants, as well as to demonstrate the relationship of this phenomenon with the effectiveness of herbicides for weed control. Relationships are described between the circadian clock and the time of application of herbicides, leaf angle and herbicide interception, as well as photosynthetic activity in response to the circadian clock and herbicide efficiency. Further, it is discussed the role of phytochrome B (phyB) in the sensitivity of plants to glyphosate herbicide. The greater understanding of the circadian clock in plants is essential to achieve greater efficiency of herbicides and hence greater control of weeds and higher crop yields.

scholarly journals The Role of Light and Circadian Clock in Regulation of Leaf Senescence

2021 ◽  
Vol 12 ◽  
Author(s):  
Juhyeon Lee ◽  
Myeong Hoon Kang ◽  
Jung Yeon Kim ◽  
Pyung Ok Lim
Keyword(s):  
Circadian Clock ◽  
Leaf Senescence ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Control Plant ◽  
Structural Features ◽  
Clock Period ◽  
Environmental Signals

Leaf senescence is an integrated response of the cells to develop age information and various environmental signals. Thus, some of the genes involved in the response to environmental changes are expected to regulate leaf senescence. Light acts not only as the primary source of energy for photosynthesis but also as an essential environmental cue that directly control plant growth and development including leaf senescence. The molecular mechanisms linking light signaling to leaf senescence have recently emerged, exploring the role of Phytochrome-Interacting Factors (PIFs) as a central player leading to diverse senescence responses, senescence-promoting gene regulatory networks (GRNs) involving PIFs, and structural features of transcription modules in GRNs. The circadian clock is an endogenous time-keeping system for the adaptation of organisms to changing environmental signals and coordinates developmental events throughout the life of the plant. Circadian rhythms can be reset by environmental signals, such as light-dark or temperature cycles, to match the environmental cycle. Research advances have led to the discovery of the role of core clock components as senescence regulators and their underlying signaling pathways, as well as the age-dependent shortening of the circadian clock period. These discoveries highlight the close relationship between the circadian system and leaf senescence. Key issues remain to be elucidated, including the effect of light on leaf senescence in relation to the circadian clock, and the identification of key molecules linking aging, light, and the circadian clock, and integration mechanisms of various senescence-affecting signals at the multi-regulation levels in dynamics point of view.

The Circadian Clock Protein CRY1 Is a Negative Regulator of HIF-11

2018 ◽  
Author(s):  
Elitsa Y. Dimova ◽  
Mirza Jakupovic ◽  
Kateryna Kubaichuk ◽  
Daniela Mennerich ◽  
Tabughang Franklin Chi ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Negative Regulator ◽  
Clock Protein

scholarly journals Circadian control of interferon-sensitive gene expression in murine skin

2020 ◽  
Vol 117 (11) ◽  
pp. 5761-5771 ◽  
Author(s):  
Elyse Noelani Greenberg ◽  
Michaela Ellen Marshall ◽  
Suoqin Jin ◽  
Sanan Venkatesh ◽  
Morgan Dragan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Mouse Skin ◽  
Time Of Day ◽  
Reciprocal Relationship ◽  
Negative Regulator ◽  
Microbial Pathogens ◽  
Feeding Time ◽  
Antitumor Effects ◽  
Human Patient

The circadian clock coordinates a variety of immune responses with signals from the external environment to promote survival. We investigated the potential reciprocal relationship between the circadian clock and skin inflammation. We treated mice topically with the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ) to activate IFN-sensitive gene (ISG) pathways and induce psoriasiform inflammation. IMQ transiently altered core clock gene expression, an effect mirrored in human patient psoriatic lesions. In mouse skin 1 d after IMQ treatment, ISGs, including the key ISG transcription factorIFN regulatory factor 7(Irf7),were more highly induced after treatment during the day than the night. Nuclear localization of phosphorylated-IRF7 was most prominently time-of-day dependent in epidermal leukocytes, suggesting that these cell types play an important role in the diurnal ISG response to IMQ. Mice lackingBmal1systemically had exacerbated and arrhythmic ISG/Irf7expression after IMQ. Furthermore, daytime-restricted feeding, which affects the phase of the skin circadian clock, reverses the diurnal rhythm of IMQ-induced ISG expression in the skin. These results suggest a role for the circadian clock, driven by BMAL1, as a negative regulator of the ISG response, and highlight the finding that feeding time can modulate the skin immune response. Since the IFN response is essential for the antiviral and antitumor effects of TLR activation, these findings are consistent with the time-of-day–dependent variability in the ability to fight microbial pathogens and tumor initiation and offer support for the use of chronotherapy for their treatment.

scholarly journals Evidence for a Putative Circadian Kiss-Clock in the Hypothalamic AVPV in Female Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (8) ◽  
pp. 2999-3011 ◽  
Author(s):  
David Chassard ◽  
Isabelle Bur ◽  
Vincent-Joseph Poirel ◽  
Jorge Mendoza ◽  
Valérie Simonneaux
Keyword(s):  
Circadian Clock ◽  
Time Of Day ◽  
Daily Rhythm ◽  
Circadian Period ◽  
Suprachiasmatic Nuclei ◽  
Intact Female ◽  
Lh Surge ◽  
Female Mice ◽  
Periventricular Nucleus ◽  
Clock Protein

Abstract The kisspeptin (Kp) neurons in the anteroventral periventricular nucleus (AVPV) are essential for the preovulatory LH surge, which is gated by circulating estradiol (E2) and the time of day. We investigated whether AVPV Kp neurons in intact female mice may be the site in which both E2 and daily signals are integrated and whether these neurons may host a circadian oscillator involved in the timed LH surge. In the afternoon of proestrous day, Kp immunoreactivity displayed a marked and transient decrease 2 hours before the LH surge. In contrast, Kp content was stable throughout the day of diestrus, when LH levels are constantly low. AVPV Kp neurons expressed the clock protein period 1 (PER1) with a daily rhythm that is phase delayed compared with the PER1 rhythm measured in the main clock of the suprachiasmatic nuclei (SCN). PER1 rhythm in the AVPV, but not in the SCN, exhibited a significant phase delay of 2.8 hours in diestrus as compared with proestrus. Isolated Kp-expressing AVPV explants from PER2::LUCIFERASE mice displayed sustained circadian oscillations of bioluminescence with a circadian period (23.2 h) significantly shorter than that of SCN explants (24.5 h). Furthermore, in AVPV explants incubated with E2 (10 nM to 1 μM), the circadian period was lengthened by 1 hour, whereas the SCN clock remained unaltered. In conclusion, these findings indicate that AVPV Kp neurons display an E2-dependent daily rhythm, which may possibly be driven by an intrinsic circadian clock acting in combination with the SCN timing signal.

scholarly journals The day/night difference in the circadian clock’s response to acute lipopolysaccharide and the rhythmic Stat3 expression in the rat suprachiasmatic nucleus

2018 ◽  
Author(s):  
Simona Moravcová ◽  
Dominika Pačesová ◽  
Barbora Melkes ◽  
Hana Kyclerová ◽  
Veronika Spišská ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Clock Genes ◽  
Activity Patterns ◽  
Night Time ◽  
Male Wistar Rats ◽  
And Function ◽  
External Signals

AbstractThe circadian clock in the suprachiasmatic nucleus (SCN) regulates daily rhythms in physiology and behaviour and is an important part of the mammalian homeostatic system. Previously, we have shown that systemic inflammatory stimulation with lipopolysaccharide (LPS) induced the daytime-dependent phosphorylation of STAT3 in the SCN. Here, we demonstrate the LPS-induced Stat3 mRNA expression in the SCN and show also the circadian rhythm in Stat3 expression in the SCN, with high levels during the day. Moreover, we examined the effects of LPS (1mg/kg), applied either during the day or the night, on the rhythm in locomotor activity of male Wistar rats. We observed that recovery of normal locomotor activity patterns took longer when the animals were injected during the night. The clock genes Per1, Per2 and Nr1d1, and phosphorylation of kinases ERK1/2 and GSK3β are sensitive to external cues and function as the molecular entry for external signals into the circadian clockwork. We also studied the immediate changes in these clock genes expressions and the phosphorylation of ERK1/2 and GSK3β in the suprachiasmatic nucleus in response to daytime or night-time inflammatory stimulation. We revealed mild and transient changes with respect to the controls. Our data stress the role of STAT3 in the circadian clock response to the LPS and provide further evidence of the interaction between the circadian clock and immune system.

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