scholarly journals Functional Role of CREB-Binding Protein in the Circadian Clock System of Drosophila melanogaster

2007 ◽  
Vol 27 (13) ◽  
pp. 4876-4890 ◽  
Author(s):  
Chunghun Lim ◽  
Jongbin Lee ◽  
Changtaek Choi ◽  
Juwon Kim ◽  
Eunjin Doh ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Cultured Cells ◽  
Clock Genes ◽  
Binding Protein ◽  
Clock Cycle ◽  
Creb Binding Protein ◽  
Locomotor Rhythm ◽  
Pigment Dispersing Factor ◽  
Clock System ◽  
Functional Relevance

ABSTRACT Rhythmic histone acetylation underlies the oscillating expression of clock genes in the mammalian circadian clock system. Cellular factors that contain histone acetyltransferase and histone deacetylase activity have been implicated in these processes by direct interactions with clock genes, but their functional relevance remains to be assessed by use of appropriate animal models. Here, using transgenic fly models, we show that CREB-binding protein (CBP) participates in the transcriptional regulation of the Drosophila CLOCK/CYCLE (dCLK/CYC) heterodimer. CBP knockdown in pigment dispersing factor-expressing cells lengthens the period of adult locomotor rhythm with the prolonged expression of period and timeless genes, while CBP overexpression in timeless-expressing cells causes arrhythmic circadian behaviors with the impaired expression of these dCLK/CYC-induced clock genes. In contrast to the mammalian circadian clock system, CBP overexpression attenuates the transcriptional activity of the dCLK/CYC heterodimer in cultured cells, possibly by targeting the PER-ARNT-SIM domain of dCLK. Our data suggest that the Drosophila circadian clock system has evolved a distinct mechanism to tightly regulate the robust transcriptional potency of the dCLK/CYC heterodimer.

scholarly journals The role of clockwork orange in the circadian clock of the cricket Gryllus bimaculatus

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Yasuaki Tomiyama ◽  
Tsugumichi Shinohara ◽  
Mirai Matsuka ◽  
Tetsuya Bando ◽  
Taro Mito ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Clock Cycle ◽  
Constant Darkness ◽  
Mrna Levels ◽  
Gryllus Bimaculatus ◽  
Locomotor Rhythm ◽  
Rhythmic Expression ◽  
Cryptochrome 2

Abstract The circadian clock generates rhythms of approximately 24 h through periodic expression of the clock genes. In insects, the major clock genes period (per) and timeless (tim) are rhythmically expressed upon their transactivation by CLOCK/CYCLE, with peak levels in the early night. In Drosophila, clockwork orange (cwo) is known to inhibit the transcription of per and tim during the daytime to enhance the amplitude of the rhythm, but its function in other insects is largely unknown. In this study, we investigated the role of cwo in the clock mechanism of the cricket Gryllus bimaculatus. The results of quantitative RT-PCR showed that under a light/dark (LD) cycle, cwo is rhythmically expressed in the optic lobe (lamina-medulla complex) and peaks during the night. When cwo was knocked down via RNA interference (RNAi), some crickets lost their locomotor rhythm, while others maintained a rhythm but exhibited a longer free-running period under constant darkness (DD). In cwoRNAi crickets, all clock genes except for cryptochrome 2 (cry2) showed arrhythmic expression under DD; under LD, some of the clock genes showed higher mRNA levels, and tim showed rhythmic expression with a delayed phase. Based on these results, we propose that cwo plays an important role in the cricket circadian clock.

Circadian clock regulates granulosa cell autophagy through NR1D1-mediated inhibition of ATG5

2021 ◽  
Author(s):  
Jing Zhang ◽  
Lijia Zhao ◽  
Yating Li ◽  
Hao Dong ◽  
Haisen Zhang ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Expression Patterns ◽  
Current Data ◽  
Orphan Receptor ◽  
Luciferase Reporter ◽  
Mobility Shift ◽  
Rhythmic Expression ◽  
Clock System ◽  
Circadian Clock Genes

Autophagy of granulosa cells (GCs) is involved in follicular atresia, which occurs repeatedly during the ovarian development cycle. Several circadian clock genes are rhythmically expressed in both rodent ovarian tissues and GCs. Nuclear receptor subfamily 1 group D member 1 (NR1D1), an important component of the circadian clock system, is involved in the autophagy process through the regulation of autophagy-related genes. However, there are no reports illustrating the role of the circadian clock system in mouse GC autophagy. In the present study, we found that core circadian clock genes (Bmal1, Per2, Nr1d1, and Dbp) and an autophagy-related gene (Atg5) exhibited rhythmic expression patterns across 24 h in mouse ovaries and primary GCs. Treatment with SR9009, an agonist of NR1D1, significantly reduced the expression of Bmal1, Per2, and Dbp in mouse GCs. ATG5 expression was significantly attenuated by SR9009 treatment in mouse GCs. Conversely, Nr1d1 knockdown increased ATG5 expression in mouse GCs. Decreased NR1D1 expression at both the mRNA and protein levels was detected in the ovaries of Bmal1-/- mice, along with elevated expression of ATG5. Dual-luciferase reporter assay and electrophoretic mobility shift assay showed that NR1D1 inhibited Atg5 transcription by binding to two putative retinoic acid-related orphan receptor response elements within the promoter. In addition, rapamycin-induced autophagy and ATG5 expression were partially reversed by SR9009 treatment in mouse GCs. Taken together, our current data demonstrated that the circadian clock regulates GC autophagy through NR1D1-mediated inhibition of ATG5 expression, and thus, plays a role in maintaining autophagy homeostasis in GCs.

Physiological and pathophysiological role of the circadian clock system

2012 ◽  
Vol 153 (35) ◽  
pp. 1370-1379 ◽  
Author(s):  
Tamás Halmos ◽  
Ilona Suba
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Biological Processes ◽  
Metabolic Processes ◽  
Hypothalamic Region ◽  
Clock System ◽  
Treatment And Prevention ◽  
Exact Function ◽  
Essential Components ◽  
Master Clock

It has been well known for ages that in living organisms the rhythmicity of biological processes is linked to the ~ 24-hour light–dark cycle. However, the exact function of the circadian clock system has been explored only in the past decades. It came to light that the photosensitive primary “master clock” is situated in the suprachiasmatic photosensitive nuclei of the special hypothalamic region, and that it is working according to ~24-hour changes of light and darkness. The master clock sends its messages to the peripheral “slave clocks”. In many organs, like pancreatic β-cells, the slave clocks have autonomic functions as well. Two essential components of the clock system are proteins encoded by the CLOCK and BMAL1 genes. CLOCK genes are in interaction with endonuclear receptors such as peroxisoma-proliferator activated receptors and Rev-erb-α, as well as with the hypothalamic-pituitary-adrenal axis, regulating the adaptation to stressors, energy supply, metabolic processes and cardiovascular system. Melatonin, the product of corpus pineale has a significant role in the functions of the clock system. The detailed discovery of the clock system has changed our previous knowledge about the development of many diseases. The most explored fields are hypertension, cardiovascular diseases, metabolic processes, mental disorders, cancers, sleep apnoe and joint disorders. CLOCK genes influence ageing as well. The recognition of the periodicity of biological processes makes the optimal dosing of certain drugs feasible. The more detailed discovery of the interaction of the clock system might further improve treatment and prevention of many disorders. Orv. Hetil., 2012, 153, 1370–1379.

scholarly journals Genomic basis of circannual rhythm in the european corn borer moth

2019 ◽  
Author(s):  
Genevieve M. Kozak ◽  
Crista B. Wadsworth ◽  
Shoshanna C. Kahne ◽  
Steven M. Bogdanowicz ◽  
Richard G. Harrison ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Circadian Clock ◽  
European Corn Borer ◽  
Molecular Mechanisms ◽  
Clock Genes ◽  
Clock Cycle ◽  
Physiological Role ◽  
Genomic Variation ◽  
Circannual Rhythm ◽  
Corn Borer

ABSTRACTGenetic variation in life-history timing allows populations to synchronize with seasonal cycles but little is known about the molecular mechanisms that produce differences in circannual rhythm in nature. Changes in diapause timing in the European corn borer moth (Ostrinia nubilalis) have facilitated rapid response to shifts in winter length encountered during range expansion and from climate change, with some populations emerging from diapause earlier to produce an additional generation per year. We identify genomic variation associated with changes in the time spent in winter diapause and show evidence that the circadian clock genes period (per) and pigment dispersing factor receptor (Pdfr) interact to underlie this adaptive polymorphism in circannual rhythm. Per and Pdfr are located within two epistatic QTL, strongly differ in allele frequency among individuals that pupate earlier or later, have the highest linkage disequilibrium among gene pairs in the QTL regions despite separation by > 4 megabases, and possess amino-acid changes likely to affect function. One per mutation in linkage disequilibrium with Pdfr creates a novel putative clock-cycle binding site found exclusively in populations that pupate later. We find associated changes in free-running daily circadian rhythm, with longer daily rhythms in individuals that end diapause early. These results support a modular connection between circadian and circannual timers and provide testable hypotheses about the physiological role of the circadian clock in seasonal synchrony. Winter length is expected to continually shorten from climate warming and we predict these gene candidates will be targets of selection for future adaptation and population persistence.

scholarly journals “A novel female-specific circadian clock mechanism regulating metabolism”

2020 ◽  
Author(s):  
Tsedey Mekbib ◽  
Ting-Chung Suen ◽  
Aisha Rollins-Hairston ◽  
Kiandra Smith ◽  
Ariel Armstrong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Cultured Cells ◽  
Clock Genes ◽  
Cholesterol Metabolism ◽  
Lipoprotein Metabolism ◽  
Circadian Clocks ◽  
Control Of Gene Expression ◽  
Female Specific

AbstractCircadian clocks enable organisms to predict and align their behaviors and physiologies to constant daily day-night environmental cycle. Because the ubiquitin ligase Siah2 has been identified as a potential regulator of circadian clock function in cultured cells, we have used Siah2-deficient mice to examine its function in vivo. Our experiments demonstrate a striking and unexpected sexually dimorphic effect of Siah2 deficiency on the regulation of rhythmically expressed genes. The absence of Siah2 in females, but not in males, altered the expression of core circadian clock genes and drastically remodeled the rhythmic hepatic transcriptome. Siah2 loss, only in females, increased the expression of 100’s of genes selectively at mid-day, resulting in a ∼70% increase in the number of rhythmically expressed genes, and shifted the expression of 100’s of other genes from a mid-night peak, to a mid-day peak. The combined result is a near inversion of overall rhythmicity in gene expression selectively in Siah2-deficient females. This dramatic reorganization created a substantial misalignment between rhythmic liver functions and feeding/behavioral rhythms, and consequently impaired daily patterns of lipid/lipoprotein metabolism and metabolic responses to high-fat diet. Collectively, our results suggest that Siah2 is part of a female-specific circadian mechanism important for maintaining metabolic homeostasis and may play a key role in the establishing sexual dimorphisms in metabolism.Signficance statementCircadian clocks drive daily rhythms in many aspects of our physiology, optimally aligning functions across the day-night cycle. How circadian clocks drives these rhythms is thought to be due to largely similar transcriptional pathways and mechanisms in males and females, although some rhythms are modulated by sex and growth hormones. In this study, we present data that uncover the surprising existence of a female-specific transcriptional mechanism that is essential for the proper rhythmic control of gene expression in the liver. Disrupting this mechanism substantially impairs the circadian regulation of lipid and cholesterol metabolism selectively in females, impairing their resistance to diet-induced obesity. These results reveal that circadian clocks may be broadly coupled to physiological rhythms using unexpected sex-specific mechanisms.

scholarly journals Insights into the Role of Circadian Rhythms in Bone Metabolism: A Promising Intervention Target?

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chao Song ◽  
Jia Wang ◽  
Brett Kim ◽  
Chanyi Lu ◽  
Zheng Zhang ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Bone Metabolism ◽  
Clock Genes ◽  
Current Knowledge ◽  
Gene Knockout ◽  
Osteoclast Differentiation ◽  
Clock System ◽  
Peripheral Oscillators ◽  
Turnover Markers

Numerous physiological processes of mammals, including bone metabolism, are regulated by the circadian clock system, which consists of a central regulator, the suprachiasmatic nucleus (SCN), and the peripheral oscillators of the BMAL1/CLOCK-PERs/CRYs system. Various bone turnover markers and bone metabolism-regulating hormones such as melatonin and parathyroid hormone (PTH) display diurnal rhythmicity. According to previous research, disruption of the circadian clock due to shift work, sleep restriction, or clock gene knockout is associated with osteoporosis or other abnormal bone metabolism, showing the importance of the circadian clock system for maintaining homeostasis of bone metabolism. Moreover, common causes of osteoporosis, including postmenopausal status and aging, are associated with changes in the circadian clock. In our previous research, we found that agonism of the circadian regulators REV-ERBs inhibits osteoclast differentiation and ameliorates ovariectomy-induced bone loss in mice, suggesting that clock genes may be promising intervention targets for abnormal bone metabolism. Moreover, osteoporosis interventions at different time points can provide varying degrees of bone protection, showing the importance of accounting for circadian rhythms for optimal curative effects in clinical treatment of osteoporosis. In this review, we summarize current knowledge about circadian rhythms and bone metabolism.

scholarly journals The BrGI Circadian Clock Gene Is Involved in the Regulation of Glucosinolates in Chinese Cabbage

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1664
Author(s):  
Nan-Sun Kim ◽  
Su-Jeong Kim ◽  
Jung-Su Jo ◽  
Jun-Gu Lee ◽  
Soo-In Lee ◽  
...  
Keyword(s):  
Transgenic Plants ◽  
Circadian Clock ◽  
Brassica Rapa ◽  
Chinese Cabbage ◽  
Clock Gene ◽  
Clock Genes ◽  
Floral Induction ◽  
Stem Elongation ◽  
Circadian Clock Gene ◽  
Clock System

Circadian clocks integrate environmental cues with endogenous signals to coordinate physiological outputs. Clock genes in plants are involved in many physiological and developmental processes, such as photosynthesis, stomata opening, stem elongation, light signaling, and floral induction. Many Brassicaceae family plants, including Chinese cabbage (Brassica rapa ssp. pekinensis), produce a unique glucosinolate (GSL) secondary metabolite, which enhances plant protection, facilitates the design of functional foods, and has potential medical applications (e.g., as antidiabetic and anticancer agents). The levels of GSLs change diurnally, suggesting a connection to the circadian clock system. We investigated whether circadian clock genes affect the biosynthesis of GSLs in Brassica rapa using RNAi-mediated suppressed transgenic Brassica rapa GIGENTEA homolog (BrGI knockdown; hereafter GK1) Chinese cabbage. GIGANTEA plays an important role in the plant circadian clock system and is related to various developmental and metabolic processes. Using a validated GK1 transgenic line, we performed RNA sequencing and high-performance liquid chromatography analyses. The transcript levels of many GSL pathway genes were significantly altered in GK1 transgenic plants. In addition, GSL contents were substantially reduced in GK1 transgenic plants. We report that the BrGI circadian clock gene is required for the biosynthesis of GSLs in Chinese cabbage plants.

scholarly journals C-Terminal Binding Protein (CtBP) Activates the Expression of E-Box Clock Genes with CLOCK/CYCLE in Drosophila

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e63113 ◽  
Author(s):  
Taichi Q. Itoh ◽  
Akira Matsumoto ◽  
Teiichi Tanimura
Keyword(s):  
Clock Genes ◽  
Binding Protein ◽  
Clock Cycle ◽  
E Box

scholarly journals ASK family kinases mediate cellular stress and redox signaling to circadian clock

2018 ◽  
Vol 115 (14) ◽  
pp. 3646-3651 ◽  
Author(s):  
Kiyomichi Imamura ◽  
Hikari Yoshitane ◽  
Kazuki Hattori ◽  
Mitsuo Yamaguchi ◽  
Kento Yoshida ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Cultured Cells ◽  
Clock Genes ◽  
Cellular Stress ◽  
Underlying Mechanism ◽  
Circadian Period ◽  
Redox States ◽  
Rhythmic Expression ◽  
Physiological Impact ◽  
Intracellular Redox

Daily rhythms of behaviors and physiologies are generated by the circadian clock, which is composed of clock genes and the encoded proteins forming transcriptional/translational feedback loops (TTFLs). The circadian clock is a self-sustained oscillator and flexibly responds to various time cues to synchronize with environmental 24-h cycles. However, the key molecule that transmits cellular stress to the circadian clockwork is unknown. Here we identified apoptosis signal-regulating kinase (ASK), a member of the MAPKKK family, as an essential mediator determining the circadian period and phase of cultured cells in response to osmotic changes of the medium. The physiological impact of ASK signaling was demonstrated by a response of the clock to changes in intracellular redox states. Intriguingly, the TTFLs drive rhythmic expression of Ask genes, indicating ASK-mediated association of the TTFLs with intracellular redox. In behavioral analysis, Ask1, Ask2, and Ask3 triple-KO mice exhibited compromised light responses of the circadian period and phase in their activity rhythms. LC-MS/MS–based proteomic analysis identified a series of ASK-dependent and osmotic stress-responsive phosphorylations of proteins, among which CLOCK, a key component of the molecular clockwork, was phosphorylated at Thr843 or Ser845 in the carboxyl-terminal region. These findings reveal the ASK-dependent stress response as an underlying mechanism of circadian clock flexibility.

scholarly journals Sleep-drive reprograms clock neuronal identity through CREB-binding protein induced PDFR expression

2019 ◽  
Author(s):  
MK Klose ◽  
PJ Shaw
Keyword(s):  
Binding Protein ◽  
Creb Binding Protein ◽  
Synaptic Scaling ◽  
Surface Receptors ◽  
Pigment Dispersing Factor ◽  
Hebbian Plasticity ◽  
Sleep Drive ◽  
Circuit Function ◽  
The Impact ◽  
Activity Dependent

AbstractNeuronal circuits can be re-modeled by Hebbian plasticity, synaptic scaling and, under some circumstances, activity-dependent respecification of cell-surface receptors. Although the impact of sleep on Hebbian plasticity and synaptic scaling are well studied, sleep’s role in receptor respecification remains unclear. We demonstrate that high sleep-pressure quickly reprograms the Drosophila wake-promoting large-ventrolateral clock-neurons to express the Pigment Dispersing Factor receptor. The addition of this signaling input into the circuit is associated with increased waking and early mating success. The respecification of Pigment Dispersing Factor receptor in both young and adult large ventrolateral neurons requires two dopamine receptors and activation of the transcriptional regulator nejire (CREB-binding protein). These data identify receptor-respecification as an important mechanism to sculpt circuit function to match sleep levels with demand.

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