Achilles-Mediated and Sex-Specific Regulation of Circadian mRNA Rhythms in Drosophila

2019 ◽  
Vol 34 (2) ◽  
pp. 131-143 ◽  
Author(s):  
Jiajia Li ◽  
Renee Yin Yu ◽  
Farida Emran ◽  
Brian E. Chen ◽  
Michael E. Hughes
Keyword(s):  
Circadian Clock ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Clock Genes ◽  
Peripheral Tissues ◽  
Knock Down ◽  
Rhythmic Expression ◽  
The Core ◽  
Physiological Processes ◽  
Specific Regulation

The circadian clock is an evolutionarily conserved mechanism that generates the rhythmic expression of downstream genes. The core circadian clock drives the expression of clock-controlled genes, which in turn play critical roles in carrying out many rhythmic physiological processes. Nevertheless, the molecular mechanisms by which clock output genes orchestrate rhythmic signals from the brain to peripheral tissues are largely unknown. Here we explored the role of one rhythmic gene, Achilles, in regulating the rhythmic transcriptome in the fly head. Achilles is a clock-controlled gene in Drosophila that encodes a putative RNA-binding protein. Achilles expression is found in neurons throughout the fly brain using fluorescence in situ hybridization (FISH), and legacy data suggest it is not expressed in core clock neurons. Together, these observations argue against a role for Achilles in regulating the core clock. To assess its impact on circadian mRNA rhythms, we performed RNA sequencing (RNAseq) to compare the rhythmic transcriptomes of control flies and those with diminished Achilles expression in all neurons. Consistent with previous studies, we observe dramatic upregulation of immune response genes upon knock-down of Achilles. Furthermore, many circadian mRNAs lose their rhythmicity in Achilles knock-down flies, suggesting that a subset of the rhythmic transcriptome is regulated either directly or indirectly by Achilles. These Achilles-mediated rhythms are observed in genes involved in immune function and in neuronal signaling, including Prosap, Nemy and Jhl-21. A comparison of RNAseq data from control flies reveals that only 42.7% of clock-controlled genes in the fly brain are rhythmic in both males and females. As mRNA rhythms of core clock genes are largely invariant between the sexes, this observation suggests that sex-specific mechanisms are an important, and heretofore under-appreciated, regulator of the rhythmic transcriptome.

scholarly journals The Plant Circadian Clock and Chromatin Modifications

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 561 ◽  
Author(s):  
Ping Yang ◽  
Jianhao Wang ◽  
Fu-Yu Huang ◽  
Songguang Yang ◽  
Keqiang Wu
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Feedback Regulation ◽  
Chromatin Modifications ◽  
Environmental Signals ◽  
The Core ◽  
Physiological Processes ◽  
Circadian Clock Genes ◽  
Rhythmic Gene ◽  
Transcriptional Feedback

The circadian clock is an endogenous timekeeping network that integrates environmental signals with internal cues to coordinate diverse physiological processes. The circadian function depends on the precise regulation of rhythmic gene expression at the core of the oscillators. In addition to the well-characterized transcriptional feedback regulation of several clock components, additional regulatory mechanisms, such as alternative splicing, regulation of protein stability, and chromatin modifications are beginning to emerge. In this review, we discuss recent findings in the regulation of the circadian clock function in Arabidopsis thaliana. The involvement of chromatin modifications in the regulation of the core circadian clock genes is also discussed.

scholarly journals Cyclic uniaxial mechanical load enhances chondrogenesis through entraining the molecular circadian clock

2021 ◽  
Author(s):  
Judit Vago ◽  
Eva Katona ◽  
Roland A. Takacs ◽  
Roza Zakany ◽  
Daan Van Der Veen ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Mechanical Load ◽  
Marker Gene ◽  
Cartilage Matrix ◽  
Limb Bud ◽  
Mechanical Stimuli ◽  
Rhythmic Expression ◽  
The Core ◽  
Chondroprogenitor Cells

Objective: The biomechanical environment plays a key role in regulating cartilage formation, but current understanding of mechanotransduction pathways in chondrogenic cells is still incomplete. Amongst the combination of external factors that control chondrogenesis are temporal cues that are governed by the cell-autonomous circadian clock. However, mechanical stimulation has not yet directly been proven to modulate chondrogenesis via entraining the circadian clock in chondroprogenitor cells. Design: The purpose of this study was to establish whether mechanical stimuli entrain the core clock in chondrogenic cells, and whether augmented chondrogenesis caused by mechanical loading was at least partially mediated by the synchronised, rhythmic expression of the core circadian clock genes, chondrogenic transcription factors, and cartilage matrix constituents. Results: We report here, for the first time, that cyclic uniaxial mechanical load applied for 1 hour for a period of 6 days entrains the molecular clockwork in chondroprogenitor cells during chondrogenesis in limb bud-derived micromass cultures. In addition to the several core clock genes, the chondrogenic markers SOX9, ACAN, and COL2A1 also followed a robust sinusoidal rhythmic expression pattern. These rhythmic conditions significantly enhanced cartilage matrix production and upregulated marker gene expression. The observed chondrogenesis-promoting effect of the mechanical environment was at least partially attributable to its entraining effect on the molecular clockwork, as co-application of the small molecule clock modulator longdaysin attenuated the stimulatory effects of mechanical load. Conclusions: Results from this study suggest that an optimal biomechanical environment enhances tissue homeostasis and histogenesis during early chondrogenesis through entraining the molecular clockwork.

scholarly journals Aging, melatonin biosynthesis, and circadian clockworks in the gastrointestinal system of the laboratory mouse

2019 ◽  
Vol 51 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Jiffin K. Paulose ◽  
Charles V. Cassone ◽  
Vincent M. Cassone
Keyword(s):  
Circadian Clock ◽  
Immune Function ◽  
Clock Genes ◽  
Laboratory Mouse ◽  
Middle Aged ◽  
Peripheral Tissues ◽  
Rhythmic Expression ◽  
Nitric Oxide Synthase 1 ◽  
Oxide Synthase ◽  
Young Mice

The gastrointestinal (GI) system is vital in its capacities for nutrient and water uptake, immune function, metabolism and detoxification, and stem-cell derived regeneration. Of significance to human health are a myriad of GI disorders associated with aging that integrate with the circadian clock. Here we present data from three groups of mice: young (3 mo old), middle aged (12 mo old), and old aged (24 mo old). Small intestine and colon samples taken every 4 h under light-dark (LD) conditions were assayed for gene expression related to molecular circadian rhythmicity, transcription, cell signaling, and immune function. Transcripts related to melatonin biosynthesis and signaling, as well as melatonin content from stool, were also included, as GI melatonin and aging have been associated in contexts outside of the circadian clock. With respect to circadian genes, the data here are congruent with data from other peripheral tissues: age does not affect the rhythmic expression of core clock genes in the gut. The same can be said for several clock-controlled transcripts. In contrast, diurnal patterns in the expression of nitric oxide synthase 1 and of immune factors irak4 and interleukin-8 were observed in the colon of young mice that were lost in middle-aged and aged animals. Furthermore, the diurnal pattern of melatonin synthesis genes was altered by age, and stool melatonin levels showed significant decline between young mice and aged cohorts. These data expand the evidence for the persistence of the circadian clock throughout the aging process and highlight its importance to health.

scholarly journals Impact of Short-Term Fasting on The Rhythmic Expression of the Core Circadian Clock and Clock-Controlled Genes in Skeletal Muscle of Crucian Carp (Carassius auratus)

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 526 ◽  
Author(s):  
Ping Wu ◽  
Lingsheng Bao ◽  
Ruiyong Zhang ◽  
Yulong Li ◽  
Li Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Circadian Rhythms ◽  
Crucian Carp ◽  
Clock Genes ◽  
Functional Genes ◽  
Short Term ◽  
Peripheral Tissues ◽  
Circadian Genes ◽  
Rhythmic Expression ◽  
The Core

The peripheral tissue pacemaker is responsive to light and other zeitgebers, especially food availability. Generally, the pacemaker can be reset and entrained independently of the central circadian structures. Studies involving clock-gene expressional patterns in fish peripheral tissues have attracted considerable attention. However, the rhythmic expression of clock genes in skeletal muscle has only scarcely been investigated. The present study was designed to investigate the core clock and functional gene expression rhythms in crucian carp. Meanwhile, the synchronized effect of food restrictions (short-term fasting) on these rhythms in skeletal muscle was carefully examined. In fed crucian carp, three core clock genes (Clock, Bmal1a, and Per1) and five functional genes (Epo, Fas, IGF1R2, Jnk1, and MyoG) showed circadian rhythms. By comparison, four core clock genes (Clock, Bmal1a, Cry3, and Per2) and six functional genes (Epo, GH, IGF2, Mstn, Pnp5a, and Ucp1) showed circadian rhythms in crucian carp muscle after 7-day fasting. In addition, three core clock genes (Clock, Per1, and Per3) and six functional genes (Ampk1a, Lpl, MyoG, Pnp5a, PPARα, and Ucp1) showed circadian rhythms in crucian carp muscle after 15-day fasting. However, all gene rhythmic expression patterns differed from each other. Furthermore, it was found that the circadian genes could be altered by feed deprivation in crucian carp muscle through the rhythms correlation analysis of the circadian genes and functional genes. Hence, food-anticipatory activity of fish could be adjusted through the food delivery restriction under a light–dark cycle. These results provide a potential application in promoting fish growth by adjusting feeding conditions and nutritional state.

The intrinsic circadian clock within the cardiomyocyte

2005 ◽  
Vol 289 (4) ◽  
pp. H1530-H1541 ◽  
Author(s):  
David J. Durgan ◽  
Margaret A. Hotze ◽  
Tara M. Tomlin ◽  
Oluwaseun Egbejimi ◽  
Christophe Graveleau ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Molecular Mechanisms ◽  
Clock Genes ◽  
Time Of Day ◽  
Pyruvate Dehydrogenase Kinase ◽  
Continuous Treatment ◽  
Rat Cardiomyocytes ◽  
Rhythmic Expression ◽  
Adult Rat ◽  
Circadian Clock Genes

Circadian clocks are intracellular molecular mechanisms that allow the cell to anticipate the time of day. We have previously reported that the intact rat heart expresses the major components of the circadian clock, of which its rhythmic expression in vivo is consistent with the operation of a fully functional clock mechanism. The present study exposes oscillations of circadian clock genes [brain and arylhydrocarbon receptor nuclear translocator-like protein 1 ( bmal1), reverse strand of the c-erbaα gene ( rev-erbaα), period 2 ( per2), albumin D-element binding protein ( dbp)] for isolated adult rat cardiomyocytes in culture. Acute (2 h) and/or chronic (continuous) treatment of cardiomyocytes with FCS (50% and 2.5%, respectively) results in rhythmic expression of circadian clock genes with periodicities of 20–24 h. In contrast, cardiomyocytes cultured in the absence of serum exhibit dramatically dampened oscillations in bmal1 and dbp only. Zeitgebers (timekeepers) are factors that influence the timing of the circadian clock. Glucose, which has been previously shown to reactivate circadian clock gene oscillations in fibroblasts, has no effect on the expression of circadian clock genes in adult rat cardiomyocytes, either in the absence or presence of serum. Exposure of adult rat cardiomyocytes to the sympathetic neurotransmitter norephinephrine (10 μM) for 2 h reinitiates rhythmic expression of circadian clock genes in a serum-independent manner. Oscillations in circadian clock genes were associated with 24-h oscillations in the metabolic genes pyruvate dehydrogenase kinase 4 ( pdk4) and uncoupling protein 3 ( ucp3). In conclusion, these data suggest that the circadian clock operates within the myocytes of the heart and that this molecular mechanism persists under standard cell culture conditions (i.e., 2.5% serum). Furthermore, our data suggest that norepinephrine, unlike glucose, influences the timing of the circadian clock within the heart and that the circadian clock may be a novel mechanism regulating myocardial metabolism.

scholarly journals Repeated evolution of circadian clock dysregulation in cavefish populations

2020 ◽  
Author(s):  
Katya L. Mack ◽  
James B. Jaggard ◽  
Jenna L. Persons ◽  
Courtney N. Passow ◽  
Bethany A. Stanhope ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Molecular Mechanisms ◽  
Biological Clock ◽  
Multiple Populations ◽  
Rhythmic Expression ◽  
The Core ◽  
Cave Environment ◽  
Repeated Evolution

AbstractCircadian rhythms are nearly ubiquitous throughout nature, suggesting they are critical for survival in diverse environments. Organisms inhabiting environments with arrhythmic days, such as caves, offer a unique opportunity to study the evolution of circadian rhythms in response to changing ecological pressures. Here we demonstrate that the cave environment has led to the repeated disruption of the biological clock across multiple populations of Mexican cavefish, with the circadian transcriptome showing widespread reductions in rhythmicity and changes to the timing of the activation/repression of genes in the core pacemaker. Then, we investigate the function of two genes with decreased rhythmic expression in cavefish. Mutants of these genes phenocopy reductions in sleep seen in multiple cave populations, suggesting a link between circadian dysregulation and sleep reduction. Altogether, our results reveal that evolution in an arrhythmic environment has resulted in dysregulation to the biological clock across multiple populations by diverse molecular mechanisms.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

scholarly journals Modulatory Effects of Circadian Rhythms in the Lung Adenocarcinoma Tumor Microenvironment

2021 ◽  
Author(s):  
Qianzhun Huang ◽  
Xiaoyang Su ◽  
Ning Fang ◽  
Jian Huang
Keyword(s):  
Tumor Microenvironment ◽  
Circadian Rhythms ◽  
Lung Adenocarcinoma ◽  
Circadian Clock ◽  
Drug Sensitivity ◽  
Molecular Mechanisms ◽  
Clock Genes ◽  
Functional Enrichment ◽  
Expression Levels ◽  
Circadian Clock Genes

Abstract Background: Dysregulated circadian dynamic balance is strongly associated with cancer development. However, biological functions of circadian rhythms in lung adenocarcinoma (LUAD) have not been elucidated. This study aimed at valuating the modulatory effects of circadian rhythms in the LUAD tumor microenvironment.Methods: Multiple open-source bioinformatics research platforms are used to comprehensively elucidate the expression level, prognosis, potential biological function, drug sensitivity, and immune microenvironment of circadian clock genes in LUAD.Results: Most circadian clock genes in LUAD are dysregulated and are strongly correlated with patient prognosis, and missense mutations at splicing sites of these genes. Besides, these genes are closely associated with some well-known cancer-related marker pathways, which are mainly involved in the inhibition of the Apoptosis, Cell cycle, and DNA Damage Response Pathway. Furthermore, functional enrichment analysis revealedthat circadian clock genes regulate transcription factor activities and circadian rhythms in LUAD tissues. As for drug sensitivity, high expression of CLOCK, CRY1, and NR1D2 as well as suppressedPER2 and CRY2 expression levels are associated with drug resistance. The expression levels of circadian clock genes in LUAD correlate with immune infiltration and are involved in the regulation of immunosuppression.Conclusions: Our multi-omics analysis provides a more comprehensive understanding of the molecular mechanisms of the circadian clock genes in LUAD and provides new insights for a more precise screening of prognostic biomarkers and immunotherapy.

scholarly journals Modeling and analysis of the impacts of jet lag on circadian rhythm and its role in tumor growth

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4877 ◽  
Author(s):  
Azka Hassan ◽  
Jamil Ahmad ◽  
Hufsah Ashraf ◽  
Amjad Ali
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Clock Genes ◽  
Damage Control ◽  
Vital Role ◽  
Biochemical Networks ◽  
Jet Lag ◽  
Peripheral Tissues ◽  
Modeling And Analysis ◽  
Circadian Clock Proteins

Circadian rhythms maintain a 24 h oscillation pattern in metabolic, physiological and behavioral processes in all living organisms. Circadian rhythms are organized as biochemical networks located in hypothalamus and peripheral tissues. Rhythmicity in the expression of circadian clock genes plays a vital role in regulating the process of cell division and DNA damage control. The oncogenic protein, MYC and the tumor suppressor, p53 are directly influenced by the circadian clock. Jet lag and altered sleep/wake schedules prominently affect the expression of molecular clock genes. This study is focused on developing a Petri net model to analyze the impacts of long term jet lag on the circadian clock and its probable role in tumor progression. The results depict that jet lag disrupts the normal rhythmic behavior and expression of the circadian clock proteins. This disruption leads to persistent expression of MYC and suppressed expression of p53. Thus, it is inferred that jet lag altered circadian clock negatively affects the expressions of cell cycle regulatory genes and contribute in uncontrolled proliferation of tumor cells.

Sign in / Sign up

Export Citation Format

Share Document