scholarly journals Intermittent Hypoxia Alters the Circadian Expression of Clock Genes in Mouse Brain and Liver

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1627
Author(s):  
Bala S. C. Koritala ◽  
Yin Yeng Lee ◽  
Shweta S. Bhadri ◽  
Laetitia S. Gaspar ◽  
Corinne Stanforth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Intermittent Hypoxia ◽  
Clock Genes ◽  
The United States ◽  
Circadian Expression ◽  
Polymerase Chain ◽  
States Experience ◽  
The Impact ◽  
The Brain

At least one-third of adults in the United States experience intermittent hypoxia (IH) due to health or living conditions. The majority of these adults suffer with sleep breathing conditions and associated circadian rhythm disorders. The impact of IH on the circadian clock is not well characterized. In the current study, we used an IH mouse model to understand the impact of IH on the circadian gene expression of the canonical clock genes in the central (the brain) and peripheral (the liver) tissues. Gene expression was measured using a Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). CircaCompare was used to evaluate the differential rhythmicity between normoxia and IH. Our observations suggested that the circadian clock in the liver was less sensitive to IH compared to the circadian clock in the brain.

scholarly journals Transcriptomal dissection of soybean circadian rhythmicity in two geographically, phenotypically and genetically distinct cultivars

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanlei Yue ◽  
Ze Jiang ◽  
Enoch Sapey ◽  
Tingting Wu ◽  
Shi Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Chromosome Structure ◽  
Clock Genes ◽  
Expression Profiles ◽  
Circadian Rhythmicity ◽  
Rna Seq ◽  
Night Time ◽  
Time Points ◽  
Circadian Clock Genes

Abstract Background In soybean, some circadian clock genes have been identified as loci for maturity traits. However, the effects of these genes on soybean circadian rhythmicity and their impacts on maturity are unclear. Results We used two geographically, phenotypically and genetically distinct cultivars, conventional juvenile Zhonghuang 24 (with functional J/GmELF3a, a homolog of the circadian clock indispensable component EARLY FLOWERING 3) and long juvenile Huaxia 3 (with dysfunctional j/Gmelf3a) to dissect the soybean circadian clock with time-series transcriptomal RNA-Seq analysis of unifoliate leaves on a day scale. The results showed that several known circadian clock components, including RVE1, GI, LUX and TOC1, phase differently in soybean than in Arabidopsis, demonstrating that the soybean circadian clock is obviously different from the canonical model in Arabidopsis. In contrast to the observation that ELF3 dysfunction results in clock arrhythmia in Arabidopsis, the circadian clock is conserved in soybean regardless of the functional status of J/GmELF3a. Soybean exhibits a circadian rhythmicity in both gene expression and alternative splicing. Genes can be grouped into six clusters, C1-C6, with different expression profiles. Many more genes are grouped into the night clusters (C4-C6) than in the day cluster (C2), showing that night is essential for gene expression and regulation. Moreover, soybean chromosomes are activated with a circadian rhythmicity, indicating that high-order chromosome structure might impact circadian rhythmicity. Interestingly, night time points were clustered in one group, while day time points were separated into two groups, morning and afternoon, demonstrating that morning and afternoon are representative of different environments for soybean growth and development. However, no genes were consistently differentially expressed over different time-points, indicating that it is necessary to perform a circadian rhythmicity analysis to more thoroughly dissect the function of a gene. Moreover, the analysis of the circadian rhythmicity of the GmFT family showed that GmELF3a might phase- and amplitude-modulate the GmFT family to regulate the juvenility and maturity traits of soybean. Conclusions These results and the resultant RNA-seq data should be helpful in understanding the soybean circadian clock and elucidating the connection between the circadian clock and soybean maturity.

scholarly journals Daily rhythms in gene expression of the human parasite Schistosoma mansoni

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kate A. Rawlinson ◽  
Adam J. Reid ◽  
Zhigang Lu ◽  
Patrick Driguez ◽  
Anna Wawer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Schistosoma Mansoni ◽  
Circadian Clock ◽  
Drug Targets ◽  
Clock Genes ◽  
Biological Rhythms ◽  
Active Phase ◽  
Egg Laying ◽  
Daily Rhythms ◽  
Metazoan Parasites

Abstract Background The consequences of the earth’s daily rotation have led to 24-h biological rhythms in most organisms. Even some parasites are known to have daily rhythms, which, when in synchrony with host rhythms, can optimise their fitness. Understanding these rhythms may enable the development of control strategies that take advantage of rhythmic vulnerabilities. Recent work on protozoan parasites has revealed 24-h rhythms in gene expression, drug sensitivity and the presence of an intrinsic circadian clock; however, similar studies on metazoan parasites are lacking. To address this, we investigated if a metazoan parasite has daily molecular oscillations, whether they reveal how these longer-lived organisms can survive host daily cycles over a lifespan of many years and if animal circadian clock genes are present and rhythmic. We addressed these questions using the human blood fluke Schistosoma mansoni that lives in the vasculature for decades and causes the tropical disease schistosomiasis. Results Using round-the-clock transcriptomics of male and female adult worms collected from experimentally infected mice, we discovered that ~ 2% of its genes followed a daily pattern of expression. Rhythmic processes included a stress response during the host’s active phase and a ‘peak in metabolic activity’ during the host’s resting phase. Transcriptional profiles in the female reproductive system were mirrored by daily patterns in egg laying (eggs are the main drivers of the host pathology). Genes cycling with the highest amplitudes include predicted drug targets and a vaccine candidate. These 24-h rhythms may be driven by host rhythms and/or generated by a circadian clock; however, orthologs of core clock genes are missing and secondary clock genes show no 24-h rhythmicity. Conclusions There are daily rhythms in the transcriptomes of adult S. mansoni, but they appear less pronounced than in other organisms. The rhythms reveal temporally compartmentalised internal processes and host interactions relevant to within-host survival and between-host transmission. Our findings suggest that if these daily rhythms are generated by an intrinsic circadian clock then the oscillatory mechanism must be distinct from that in other animals. We have shown which transcripts oscillate at this temporal scale and this will benefit the development and delivery of treatments against schistosomiasis.

scholarly journals THE LEPTIN GENE IS A MARKER FOR THE CELL THERAPY OF METABOLIC SYNDROME

Biomeditsina ◽  
2019 ◽  
pp. 12-22
Author(s):  
N. V. Petrova
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Cell Therapy ◽  
Bone Marrow Cells ◽  
Liver And Pancreas ◽  
A Cell ◽  
Polymerase Chain ◽  
Lep Gene ◽  
The Brain

It is shown that the level of the Lep gene expression is a marker for B/Ks-Leprᵈᵇ/+ mice, which line serves as an optimal model for describing metabolic syndrome (MS) in preclinical studies. Mice were transplanted with cultured isogenic bone marrow cells (BMC) from heterozygous db/+ donors. The recipients were divided into two groups according to an early or advanced stage of MS development. We analyzed the expression of the Lep gene on the 3rd, 8th and 14th day following the administration of stem BMCs in the brain, liver and pancreas cells by polymerase chain reaction (PCR) in real time. The Lep gene expression was evaluated in terms of the number of cDNA copies. According to our data, leptin is a complete regulator of metabolic processes due to its effect on the hypothalamus, which, together with the hippocampus, controls the production of acetylcholine and insulin in the brain. We have proven the role of the Lep gene as a quantitative criterion for evaluating the effi cacy of a cell therapy in MS.

The Circadian Clock inArabidopsisRoots Is a Simplified Slave Version of the Clock in Shoots

Science ◽  
2008 ◽  
Vol 322 (5909) ◽  
pp. 1832-1835 ◽  
Author(s):  
Allan B. James ◽  
José A. Monreal ◽  
Gillian A. Nimmo ◽  
Ciarán L. Kelly ◽  
Pawel Herzyk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Circadian Clock ◽  
Clock Genes ◽  
Plant Cells ◽  
Feedback Loops ◽  
Circadian Oscillator ◽  
Inhibit Gene Expression ◽  
Organ Specific ◽  
Plant Clock

The circadian oscillator in eukaryotes consists of several interlocking feedback loops through which the expression of clock genes is controlled. It is generally assumed that all plant cells contain essentially identical and cell-autonomous multiloop clocks. Here, we show that the circadian clock in the roots of matureArabidopsisplants differs markedly from that in the shoots and that the root clock is synchronized by a photosynthesis-related signal from the shoot. Two of the feedback loops of the plant circadian clock are disengaged in roots, because two key clock components, the transcription factors CCA1 and LHY, are able to inhibit gene expression in shoots but not in roots. Thus, the plant clock is organ-specific but not organ-autonomous.

CORTISOL CIRCADIAN RHYTHM AND INSULIN RESISTANCE IN MUSCLE: EFFECT OF DOSING AND TIMING OF HYDROCORTISONE EXPOSURE ON INSULIN SENSITIVITY IN SYNCHRONIZED MUSCLE CELLS.

2020 ◽  
Author(s):  
Mariarosaria Negri ◽  
Claudia Pivonello ◽  
Chiara Simeoli ◽  
Gilda Di Gennaro ◽  
Mary Anna Venneri ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Circadian Rhythm ◽  
Insulin Sensitivity ◽  
Circadian Clock ◽  
Insulin Signaling ◽  
Clock Genes ◽  
Muscle Cells ◽  
C2c12 Cells ◽  
Circadian Expression

Introduction/Aim: Circadian rhythm disruption is emerging as a risk factor for metabolic disorders and particularly, alterations in clock genes circadian expression have been shown to influence insulin sensitivity. Recently, the reciprocal interplay between the circadian clock machinery and HPA axis has been largely demonstrated: the circadian clock may control the physiological circadian endogenous glucocorticoids secretion and action; glucocorticoids, in turn, are potent regulator of the circadian clock and their inappropriate replacement has been associated with metabolic impairment. The aim of the current study was to investigate in vitro the interaction between the timing-of-the-day exposure to different hydrocortisone (HC) concentrations on muscle insulin sensitivity. Methods: Serum-shock synchronized mouse skeletal muscle C2C12 cells were exposed to different HC concentrations recapitulating the circulating daily physiological cortisol profile (standard cortisol profile), the circulating daily cortisol profile that reached in adrenal insufficient (AI) patients treated with once-daily MR-HC (flat cortisol profile) and treated with thrice-daily of conventional IR-HC (steep cortisol profile). The 24 hrs spontaneous oscillation of the clock genes in synchronized C2C12 cells was used to align the timing for in vitro HC exposure (Bmal1 acrophase, midphase and bathyphase) with the reference times of cortisol peaks in AI treated with IR-HC (8 am, 1 pm, 6 pm). A panel of 84 insulin sensitivity related genes and intracellular insulin signaling proteins were analyzed by RT-qPCR and western blot, respectively. Results: Only the steep profile, characterized by a higher HC exposure during Bmal1 bathyphase, produced significant downregulation in 21 insulin sensitivity-related genes. Among these, Insr, Irs1, Irs2, Pi3kca and Adipor2 were downregulated when compared the flat to the standard or steep profile. Reduced intracellular IRS1 Tyr608, AKT Ser473, AMPK Thr172 and ACC Ser79 phosphorylations were also observed. Conclusions: The current study demonstrated that is late-in-the-day cortisol exposure that modulates insulin sensitivity-related genes expression and intracellular insulin signaling in skeletal muscle cells.

scholarly journals The Impact of the Circadian Genes CLOCK and ARNTL on Myocardial Infarction

2020 ◽  
Vol 9 (2) ◽  
pp. 484
Author(s):  
Ivana Škrlec ◽  
Jakov Milić ◽  
Robert Steiner
Keyword(s):  
Myocardial Infarction ◽  
Circadian Clock ◽  
Case Control Study ◽  
Clock Genes ◽  
Physiological Mechanisms ◽  
Chi Square ◽  
Chi Square Test ◽  
Circadian Clock Genes ◽  
The Impact ◽  
Control Study

The circadian rhythm regulates various physiological mechanisms, and its disruption can promote many disorders. Disturbance of endogenous circadian rhythms enhances the chance of myocardial infarction (MI), showing that circadian clock genes could have a crucial function in the onset of the disease. This case-control study was performed on 1057 participants. It was hypothesized that the polymorphisms of one nucleotide (SNP) in three circadian clock genes (CLOCK, ARNTL, and PER2) could be associated with MI. Statistically significant differences, estimated by the Chi-square test, were found in the distribution of alleles and genotypes between MI and no-MI groups of the CLOCK (rs6811520 and rs13124436) and ARNTL (rs3789327 and rs12363415) genes. According to the results of the present study, the polymorphisms in the CLOCK and ARNTL genes could be related to MI.

scholarly journals Region-specific Foxp2 deletions in cortex, striatum or cerebellum cannot explain vocalization deficits observed in spontaneous global knockouts

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Bastiaan H. A. Urbanus ◽  
Saša Peter ◽  
Simon E. Fisher ◽  
Chris I. De Zeeuw
Keyword(s):  
Gene Expression ◽  
Language Comprehension ◽  
Motor Performance ◽  
Broadband Noise ◽  
Conditional Knockout ◽  
Ultrasonic Vocalizations ◽  
Rare Mutations ◽  
Key Sites ◽  
The Impact ◽  
The Brain

AbstractFOXP2 has been identified as a gene related to speech in humans, based on rare mutations that yield significant impairments in speech at the level of both motor performance and language comprehension. Disruptions of the murine orthologue Foxp2 in mouse pups have been shown to interfere with production of ultrasonic vocalizations (USVs). However, it remains unclear which structures are responsible for these deficits. Here, we show that conditional knockout mice with selective Foxp2 deletions targeting the cerebral cortex, striatum or cerebellum, three key sites of motor control with robust neural gene expression, do not recapture the profile of pup USV deficits observed in mice with global disruptions of this gene. Moreover, we observed that global Foxp2 knockout pups show substantive reductions in USV production as well as an overproduction of short broadband noise “clicks”, which was not present in the brain region-specific knockouts. These data indicate that deficits of Foxp2 expression in the cortex, striatum or cerebellum cannot solely explain the disrupted vocalization behaviours in global Foxp2 knockouts. Our findings raise the possibility that the impact of Foxp2 disruption on USV is mediated at least in part by effects of this gene on the anatomical prerequisites for vocalizing.

scholarly journals SPF45-related splicing factor for phytochrome signaling promotes photomorphogenesis by regulating pre-mRNA splicing in Arabidopsis

2017 ◽  
Vol 114 (33) ◽  
pp. E7018-E7027 ◽  
Author(s):  
Ruijiao Xin ◽  
Ling Zhu ◽  
Patrice A. Salomé ◽  
Estefania Mancini ◽  
Carine M. Marshall ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Molecular Mechanisms ◽  
Fluorescent Protein ◽  
Clock Genes ◽  
Mrna Processing ◽  
Mrna Splicing ◽  
Splicing Factor ◽  
Light Signaling ◽  
Small Nuclear Ribonucleoprotein

Light signals regulate plant growth and development by controlling a plethora of gene expression changes. Posttranscriptional regulation, especially pre-mRNA processing, is a key modulator of gene expression; however, the molecular mechanisms linking pre-mRNA processing and light signaling are not well understood. Here we report a protein related to the human splicing factor 45 (SPF45) named splicing factor for phytochrome signaling (SFPS), which directly interacts with the photoreceptor phytochrome B (phyB). In response to light, SFPS-RFP (red fluorescent protein) colocalizes with phyB-GFP in photobodies. sfps loss-of-function plants are hyposensitive to red, far-red, and blue light, and flower precociously. SFPS colocalizes with U2 small nuclear ribonucleoprotein-associated factors including U2AF65B, U2A′, and U2AF35A in nuclear speckles, suggesting SFPS might be involved in the 3′ splice site determination. SFPS regulates pre-mRNA splicing of a large number of genes, of which many are involved in regulating light signaling, photosynthesis, and the circadian clock under both dark and light conditions. In vivo RNA immunoprecipitation (RIP) assays revealed that SFPS associates with EARLY FLOWERING 3 (ELF3) mRNA, a critical link between light signaling and the circadian clock. Moreover, PHYTOCHROME INTERACTING FACTORS (PIFs) transcription factor genes act downstream of SFPS, as the quadruple pif mutant pifq suppresses defects of sfps mutants. Taken together, these data strongly suggest SFPS modulates light-regulated developmental processes by controlling pre-mRNA splicing of light signaling and circadian clock genes.

scholarly journals Changes in ambient temperature are the prevailing cue in determining Brachypodium distachyon diurnal gene regulation

2019 ◽  
Author(s):  
Kirk J-M. MacKinnon ◽  
Benjamin J. Cole ◽  
Chang Yu ◽  
Joshua H. Coomey ◽  
Nolan T. Hartwick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Circadian Clock ◽  
Clock Genes ◽  
Brachypodium Distachyon ◽  
Regulation Of Gene Expression ◽  
Enrichment Analysis ◽  
Grass Species ◽  
List Type ◽  
Sequence Motifs

SUMMARYPlants are continuously exposed to diurnal fluctuations in light and temperature, and spontaneous changes in their physical or biotic environment. The circadian clock coordinates regulation of gene expression with a 24-hour period, enabling the anticipation of these events.We used RNA sequencing to characterize the Brachypodium distachyon transcriptome under light and temperature cycles, as well as under constant conditions.Approximately 3% of the transcriptome was regulated by the circadian clock, a smaller proportion reported in most other species. For most transcripts that were rhythmic under all conditions, including many known clock genes, the period of gene expression lengthened from 24 to 27 h in the absence of external cues. To functionally characterize the cyclic transcriptome in B. distachyon, we used Gene Ontology enrichment analysis, and found several terms significantly associated with peak expression at particular times of the day. Furthermore we identified sequence motifs enriched in the promoters of similarly-phased genes, some potentially associated with transcription factors.When considering the overlap in rhythmic gene expression and specific pathway behavior, thermocycles was the prevailing cue that controlled diurnal gene regulation. Taken together, our characterization of the rhythmic B. distachyon transcriptome represents a foundational resource with implications in other grass species.

scholarly journals Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms

2020 ◽  
Author(s):  
Yangbo Xiao ◽  
Ye Yuan ◽  
Mariana Jimenez ◽  
Neeraj Soni ◽  
Swathi Yadlapalli
Keyword(s):  
Gene Expression ◽  
Circadian Rhythms ◽  
Nuclear Envelope ◽  
Circadian Clock ◽  
Clock Genes ◽  
Circadian Clocks ◽  
Spatiotemporal Organization ◽  
Clock Proteins ◽  
Expression Behavior ◽  
Clock Protein

ABSTRACTCircadian clocks regulate ∼24 hour oscillations in gene expression, behavior, and physiology. While the molecular and neural mechanisms of circadian rhythms are well characterized, how cellular organization of clock components controls circadian clock regulation remains poorly understood. Here, we elucidate how clock proteins regulate circadian rhythms by controlling the spatiotemporal organization of clock genes. Using high-resolution live imaging techniques we demonstrate that Drosophila clock proteins are concentrated in a few discrete foci and are organized at the nuclear envelope; these results are in contrast to longstanding expectations that clock proteins are diffusely distributed in the nucleus. We also show that clock protein foci are highly dynamic and change in number, size, and localization over the circadian cycle. Further, we demonstrate that clock genes are positioned at the nuclear periphery by the clock proteins precisely during the circadian repression phase, suggesting that subnuclear localization of clock genes plays an important role in the control of rhythmic gene expression. Finally, we show that Lamin B receptor, a nuclear envelope protein, is required for peripheral localization of clock protein foci and clock genes and for normal circadian rhythms. These results reveal that clock proteins form dynamic nuclear foci and play a hitherto unexpected role in the subnuclear reorganization of clock genes to control circadian rhythms, identifying a novel mechanism of circadian regulation. Our results further suggest a new role for clock protein foci in the clustering of clock-regulated genes during the repression phase to control gene co-regulation and circadian rhythms.SIGNIFICANCEAlmost all living organisms have evolved circadian clocks to tell time. Circadian clocks regulate ∼24-hour oscillations in gene expression, behavior and physiology. Here, we reveal the surprisingly sophisticated spatiotemporal organization of clock proteins and clock genes and its critical role in circadian clock function. We show, in contrast to current expectations, that clock proteins are concentrated in a few discrete, dynamic nuclear foci at the nuclear envelope during the repression phase. Further, we uncovered several unexpected features of clock protein foci, including their role in positioning the clock genes at the nuclear envelope precisely during the repression phase to enable circadian rhythms. These studies provide fundamental new insights into the cellular mechanisms of circadian rhythms and establish direct links between nuclear organization and circadian clocks.

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