scholarly journals Global Age-Specific Patterns of Cyclic Gene Expression Revealed by Tunicate Transcriptome Atlas

2020 ◽  
Author(s):  
Yotam Voskoboynik ◽  
Aidan Glina ◽  
Mark Kowarsky ◽  
Chiara Anselmi ◽  
Norma F Neff ◽  
...  

AbstractExpression levels of circadian clock genes, which regulate 24-hour rhythms of behavior and physiology, have been shown to change with age. However, a study holistically linking aging and circadian gene expression is missing. Using the colonial chordate Botryllus schlosseri, we combined transcriptome sequencing and stem cell-mediated aging phenomena to test how circadian gene expression changes with age. This revealed that B. schlosseri clock and clock-controlled genes oscillate organism-wide, with daily, age-specific amplitudes and frequencies. These age-related, circadian patterns persist at the tissue level, where dramatic variations in cyclic gene expression of tissue profiles link to morphological and cellular aging phenotypes. Similar cyclical expression differences were found in hundreds of pathways associated with known hallmarks of aging, as well as pathways that were not previously linked to aging. The atlas we developed points to alterations in circadian gene expression as a key regulator of aging.One Sentence SummaryThe Ticking Clock: Systemic changes in circadian gene expression correlates with wide-ranging phenotypes of aging

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanlei Yue ◽  
Ze Jiang ◽  
Enoch Sapey ◽  
Tingting Wu ◽  
Shi Sun ◽  
...  

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.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A66-A67
Author(s):  
Audrey L Earnhardt ◽  
David G Riley ◽  
Noushin Ghaffari ◽  
Penny K Riggs ◽  
Charles R Long ◽  
...  

Abstract The primary objective of this investigation was to determine whether circadian clock genes were differentially expressed within or among bovine hypothalamic paraventricular nucleus (PVN), anterior pituitary gland (AP), adrenocortical (AC) and adrenomedullary (AM) tissues. The PVN, AP, AC, and AM were isolated from 5-yr-old Brahman cows (n = 8) harvested humanely at an abattoir between 0800-1100 h. Expression of target genes in each sample was evaluated via RNA-sequencing analyses. Gene counts were normalized using the trimmed mean of M values (TMM) method in the edgeR Package from Bioconductor, R. The normalized gene counts of genes important for circadian rhythm were statistically analyzed using the GLM Procedure of SAS. The genes analyzed were circadian locomotor output cycles protein kaput (CLOCK), cryptochrome circadian regulator 1 and 2 (CRY1 and CRY2), aryl hydrocarbon receptor nuclear translocator like (ARNTL), period circadian regulator 1 and 2 (PER1 and PER2), neuronal PAS domain protein 2 (NPAS2), and nuclear receptor subfamily 1 group D member 1 (NR1D1). Overall, relative expression profiles of clock genes differed (P < 0.01) within each tissue with PER1 having greater expression in all tissues (P < 0.01). Within the PVN expression of CLOCK, CRY1, ARNTL, and PER2 was less than that of CRY2, NPAS2, and NR1D1 (P < 0.01). In the AP, with the exception of PER1, no other clock gene differed in degree of expression. In the AC, expression of CLOCK and NPAS2 was greater than CRY1, ARNTL, PER2, and NR1D1 (P < 0.05), whereas CRY2 expression exceeded only CRY1 (P < 0.05). Within the AM, CLOCK and CRY2 expression was greater than CRY1 and ARNTL (P < 0.05). Overall, clock gene expression among tissues differed (P < 0.01) for each individual clock gene. The AC and AM had similar clock gene expression, except expression of CRY2 and PER2 was greater in AM (P < 0.05). The AC and AM had greater expression of CLOCK than the PVN and AP (P < 0.01), with PVN having greater expression than AP (P < 0.01). The AP had greater expression of NPAS2, followed by PVN, with the least expression in the AC and AM (P < 0.01). Both PVN and AP had greater CRY1 and NR1D1 expression than AC or AM (P < 0.01). The AP had greater PER1 expression than PVN, AC, and AM (P < 0.01), whereas PVN, AC, and AM had greater ARNTL expression than AP (P < 0.05). Both AP and AM had greater expression of PER2 than PVN or AC (P < 0.01). The PVN had greater expression of CRY2 than the AP, AC, and AM (P < 0.01). These results indicated that within each tissue the various clock genes were expressed in different quantities. Also, the clock genes were expressed differentially among the tissues of the bovine neuroendocrine adrenal system. Temporal relationships of these genes with the primary endocrine products of these tissues should be investigated to define the roles of peripheral clock genes in regulation of metabolism and health.


Circulation ◽  
2001 ◽  
Vol 104 (15) ◽  
pp. 1746-1748 ◽  
Author(s):  
Hidemi Nonaka ◽  
Noriaki Emoto ◽  
Koji Ikeda ◽  
Hiroyuki Fukuya ◽  
Mohammad Saifur Rohman ◽  
...  

2007 ◽  
Vol 22 (4) ◽  
pp. 254-260 ◽  
Author(s):  
Kyoe Tanaka ◽  
Naoto Ashizawa ◽  
Hiroaki Kawano ◽  
Osami Sato ◽  
Shinji Seto ◽  
...  

2010 ◽  
Vol 298 (3) ◽  
pp. R635-R641 ◽  
Author(s):  
Tao Wu ◽  
Yinhua Ni ◽  
Yue Dong ◽  
Jiafeng Xu ◽  
Xiaohong Song ◽  
...  

Although studies involving the circadian response to external time cues indicate that the peripheral clocks are dominated mainly by food cues, whether and how changes in the light and food cues affect the circadian rhythm of the renal clock is still largely unknown. In the present study, we found that the circadian phases of Bmal1, Clock, Cry1, Per1, and Per2 were altered differently by the stimuli of food and light cues in the kidney. After the individual reversal of the light-dark (LD) cycle for 7 days, Per1 displayed a 4-h phase delay, whereas the peak phases of Bmal1, Clock, Cry1 and Per2 almost remained the same as those in the control condition. With regard to the feeding-induced circadian resetting of the renal clock, we found that the resetting processes of clock genes could not be completed within 7 days, suggesting a weak synchronization effect of the food cue on the renal circadian clock. Moreover, the reentrainment of the clock genes was greatly enhanced after the reversal of both the feeding schedule and the LD cycle. Noticeably, the phases of Per1 and Clock were shifted most rapidly by 12 h within 3 days after the simultaneous reversal of the feeding schedule and the LD cycle, whereas their peak phases were only shifted by 4 h and 8 h, respectively, on the 7th day after the individual reversal of the feeding schedule. Thus Per1 and Clock may play important roles in the light-induced resetting of the circadian rhythms in the kidney.


2020 ◽  
Author(s):  
Colas Droin ◽  
Jakob El Kholtei ◽  
Keren Bahar Halpern ◽  
Clémence Hurni ◽  
Milena Rozenberg ◽  
...  

AbstractThe mammalian liver performs key physiological functions for maintaining energy and metabolic homeostasis. Liver tissue is both spatially structured and temporally orchestrated. Hepatocytes operate in repeating anatomical units termed lobules and different lobule zones perform distinct functions. The liver is also subject to extensive temporal regulation, orchestrated by the interplay of the circadian clock, systemic signals and feeding rhythms. Liver zonation was previously analyzed as a static phenomenon and liver chronobiology at the tissue level. Here, we use single-cell RNA-seq to investigate the interplay between gene regulation in space and time. Categorizing mRNA expression profiles using mixed-effect models and smFISH validations, we find that many genes in the liver are both zonated and rhythmic, most of them showing multiplicative space-time effects. Such dually regulated genes cover key hepatic functions such as lipid, carbohydrate and amino acid metabolism, but also genes not previously associated with liver zonation such as chaperones. Our data also suggest that rhythmic and localized expression of Wnt targets could be explained by rhythmically expressed Wnt ligands from non-parenchymal cells near the central vein. Core circadian clock genes are expressed in a non-zonated manner, indicating that the liver clock is robust to zonation. Together, our comprehensive scRNA-seq analysis revealed how liver function is compartmentalized spatio-temporally at the sub-lobular scale.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3348 ◽  
Author(s):  
Wen-Kai Li ◽  
Huan Li ◽  
Yuan-Fu Lu ◽  
Ying-Ying Li ◽  
Zidong Donna Fu ◽  
...  

Aim Atorvastatin is a HMG-CoA reductase inhibitor used for hyperlipidemia. Atorvastatin is generally safe but may induce cholestasis. The present study aimed to examine the effects of atorvastatin on hepatic gene expression related to bile acid metabolism and homeostasis, as well as the expression of circadian clock genes in livers of mice. Methods Adult male mice were given atorvastatin (10, 30, and 100 mg/kg, po) daily for 30 days, and blood biochemistry, histopathology, and gene expression were examined. Results Repeated administration of atorvastatin did not affect animal body weight gain or liver weights. Serum enzyme activities were in the normal range. Histologically, the high dose of atorvastatin produced scattered swollen hepatocytes, foci of feathery-like degeneration, together with increased expression of Egr-1 and metallothionein-1. Atorvastatin increased the expression of Cyp7a1 in the liver, along with FXR and SHP. In contract, atorvastatin decreased the expression of bile acid transporters Ntcp, Bsep, Ostα, and Ostβ. The most dramatic change was the 30-fold induction of Cyp7a1. Because Cyp7a1 is a circadian clock-controlled gene, we further examined the effect of atorvastatin on clock gene expression. Atorvastatin increased the expression of clock core master genes Bmal1 and Npas2, decreased the expression of clock feedback genes Per2, Per3, and the clock targeted genes Dbp and Tef, whereas it had no effect on Cry1 and Nr1d1 expression. Conclusion Repeated administration of atorvastatin affects bile acid metabolism and markedly increases the expression of the bile acid synthesis rate-limiting enzyme gene Cyp7a1, together with alterations in the expression of circadian clock genes.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anke Schwarzenberger ◽  
Luxi Chen ◽  
Linda C. Weiss

AbstractDiapause is a mechanism necessary for survival in arthropods. Often diapause induction and resurrection is light-dependent and therefore dependent on the photoperiod length and on the number of consecutive short-days. In many organisms, including the microcrustacean Daphnia magna, one functional entity with the capacity to measure seasonal changes in day-length is the circadian clock. There is a long-standing discussion that the circadian clock also controls photoperiod-induced diapause. We tested this hypothesis in D. magna, an organism which goes into a state of suspended animation with the shortening of the photoperiod. We measured gene expression of clock genes in diapause-destined embryos of D. magna in the initiation, resting and resurrection phases and checked it against gene expression levels of continuously developing embryos. We demonstrate that some genes of the clock are differentially expressed during diapause induction but not during its maintenance. Furthermore, the photoreceptor gene cry2 and the clock-associated gene brp are highly expressed during induction and early diapause, probably in order to produce excess mRNA to prepare for immediate resurrection. After resurrection, both types of embryos show a similar pattern of gene expression during development. Our study contributes significantly to the understanding of the molecular basis of diapause induction, maintenance and termination.


2015 ◽  
Vol 100 (9) ◽  
pp. E1255-E1261 ◽  
Author(s):  
Jonathan Cedernaes ◽  
Megan E. Osler ◽  
Sarah Voisin ◽  
Jan-Erik Broman ◽  
Heike Vogel ◽  
...  

Context: Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation. Objective: This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness. Intervention: In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230–0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined. Main Outcome Measures: In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (−18%; P = .033) and CRY1 (−22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 ± 932 vs 3178 ± 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 ± 1.63 vs 6.59 ± 1.32 mmol/L; P = .011). Conclusions: Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2756
Author(s):  
Julianie De La Cruz Minyety ◽  
Dorela D. Shuboni-Mulligan ◽  
Nicole Briceno ◽  
Demarrius Young ◽  
Mark R. Gilbert ◽  
...  

Circadian clock genes have been linked to clinical outcomes in cancer, including gliomas. However, these studies have not accounted for established markers that predict the prognosis, including mutations in Isocitrate Dehydrogenase (IDH), which characterize the majority of lower-grade gliomas and secondary high-grade gliomas. To demonstrate the connection between circadian clock genes and glioma outcomes while accounting for the IDH mutational status, we analyzed multiple publicly available gene expression datasets. The unsupervised clustering of 13 clock gene transcriptomic signatures from The Cancer Genome Atlas showed distinct molecular subtypes representing different disease states and showed the differential prognosis of these groups by a Kaplan–Meier analysis. Further analyses of these groups showed that a low period (PER) gene expression was associated with the negative prognosis and enrichment of the immune signaling pathways. These findings prompted the exploration of the relationship between the microenvironment and clock genes in additional datasets. Circadian clock gene expression was found to be differentially expressed across the anatomical tumor location and cell type. Thus, the circadian clock expression is a potential predictive biomarker in glioma, and further mechanistic studies to elucidate the connections between the circadian clock and microenvironment are warranted.


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