scholarly journals Circadian Regulation of a Drosophila Homolog of the Mammalian Clock Gene: PER and TIM Function as Positive Regulators

1998 ◽  
Vol 18 (10) ◽  
pp. 6142-6151 ◽  
Author(s):  
Kiho Bae ◽  
Choogon Lee ◽  
David Sidote ◽  
Keng-yu Chuang ◽  
Isaac Edery
Keyword(s):  
Circadian Clock ◽  
Clock Gene ◽  
Clock Genes ◽  
Temporal Regulation ◽  
Helix Loop Helix ◽  
Circadian Oscillators ◽  
Drosophila Homolog ◽  
Circadian Clock Genes ◽  
Positive Regulators

ABSTRACT The Clock gene plays an essential role in the manifestation of circadian rhythms (≅24 h) in mice and is a member of the basic helix-loop-helix (bHLH) PER-ARNT-SIM (PAS) superfamily of transcription factors. Here we report the characterization of a novelDrosophila bHLH-PAS protein that is highly homologous to mammalian CLOCK. (Similar findings were recently described by Allada et al. Cell 93:791–804, 1998, and Darlington et al., Science 280:1599–1603, 1998.) Transcripts from this putative Clockortholog (designated dClock) undergo daily rhythms in abundance that are antiphase to the cycling observed for the RNA products from the Drosophila melanogaster circadian clock genes period (per) and timeless(tim). Furthermore, dClock RNA cycling is abolished and the levels are at trough values in the absence of either PER or TIM, suggesting that these two proteins can function as transcriptional activators, a possibility which is in stark contrast to their previously characterized role in transcriptional autoinhibition. Finally, the temporal regulation of dClock expression is quickly perturbed by shifts in light-dark cycles, indicating that this molecular rhythm is closely connected to the photic entrainment pathway. The isolation of a Drosophila homolog ofClock together with the recent discovery of mammalian homologs of per indicate that there is high structural conservation in the integral components underlying circadian oscillators in Drosophila and mammals. Nevertheless, because mammalian Clock mRNA is constitutively expressed, our findings are a further example of striking differences in the regulation of putative circadian clock orthologs in different species.

scholarly journals The Molecular Evolution of Circadian Clock Genes in Spotted Gar (Lepisosteus oculatus)

Genes ◽  
2019 ◽  
Vol 10 (8) ◽  
pp. 622 ◽  
Author(s):  
Yi Sun ◽  
Chao Liu ◽  
Moli Huang ◽  
Jian Huang ◽  
Changhong Liu ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Teleost Fish ◽  
Clock Gene ◽  
Genome Duplication ◽  
Clock Genes ◽  
Gene Families ◽  
Regulatory Mechanisms ◽  
Spotted Gar ◽  
Circadian Clock Genes ◽  
Lepisosteus Oculatus

Circadian rhythms are biological rhythms with a period of approximately 24 h. While canonical circadian clock genes and their regulatory mechanisms appear highly conserved, the evolution of clock gene families is still unclear due to several rounds of whole genome duplication in vertebrates. The spotted gar (Lepisosteus oculatus), as a non-teleost ray-finned fish, represents a fish lineage that diverged before the teleost genome duplication (TGD), providing an outgroup for exploring the evolutionary mechanisms of circadian clocks after whole-genome duplication. In this study, we interrogated the spotted gar draft genome sequences and found that spotted gar contains 26 circadian clock genes from 11 families. Phylogenetic analysis showed that 9 of these 11 spotted gar circadian clock gene families have the same number of genes as humans, while the members of the nfil3 and cry families are different between spotted gar and humans. Using phylogenetic and syntenic analyses, we found that nfil3-1 is conserved in vertebrates, while nfil3-2 and nfil3-3 are maintained in spotted gar, teleost fish, amphibians, and reptiles, but not in mammals. Following the two-round vertebrate genome duplication (VGD), spotted gar retained cry1a, cry1b, and cry2, and cry3 is retained in spotted gar, teleost fish, turtles, and birds, but not in mammals. We hypothesize that duplication of core clock genes, such as (nfil3 and cry), likely facilitated diversification of circadian regulatory mechanisms in teleost fish. We also found that the transcription factor binding element (Ahr::Arnt) is retained only in one of the per1 or per2 duplicated paralogs derived from the TGD in the teleost fish, implicating possible subfuctionalization cases. Together, these findings help decipher the repertoires of the spotted gar’s circadian system and shed light on how the vertebrate circadian clock systems have evolved.

scholarly journals Poor Sleep Quality Is Associated with Dawn Phenomenon and Impaired Circadian Clock Gene Expression in Subjects with Type 2 Diabetes Mellitus

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yuxin Huang ◽  
Haidong Wang ◽  
Yuan Li ◽  
Xiaoming Tao ◽  
Jiao Sun
Keyword(s):  
Sleep Quality ◽  
Circadian Clock ◽  
Clock Gene ◽  
Clock Genes ◽  
Poor Sleep ◽  
Poor Sleep Quality ◽  
Clock Gene Expression ◽  
Dawn Phenomenon ◽  
Circadian Clock Genes ◽  
Good Sleep

Aims. We investigated whether poor sleep quality is associated with both dawn phenomenon and impaired circadian clock gene expression in subjects with diabetes. Methods. 81 subjects with diabetes on continuous glucose monitoring were divided into two groups according to the Pittsburgh Sleep Quality Index. The magnitude of dawn phenomenon was quantified by its increment from nocturnal nadir to prebreakfast. Peripheral leucocytes were sampled from 81 subjects with diabetes and 28 normal controls at 09:00. Transcript levels of circadian clock genes (BMAL1, PER1, PER2, and PER3) were determined by real-time quantitative polymerase chain reaction. Results. The levels of HbA1c and fasting glucose and the magnitude of dawn phenomenon were significantly higher in the diabetes group with poor sleep quality than that with good sleep quality. Peripheral leucocytes from subjects with poor sleep quality expressed significantly lower transcript levels of BMAL1 and PER1 compared with those with good sleep quality. Poor sleep quality was significantly correlated with magnitude of dawn phenomenon. Multiple linear regression showed that sleep quality and PER1 were significantly independently correlated with dawn phenomenon. Conclusions. Dawn phenomenon is associated with sleep quality. Furthermore, mRNA expression of circadian clock genes is dampened in peripheral leucocytes of subjects with poor sleep quality.

scholarly journals Differential Expression of Circadian Clock Genes in the Bovine Neuroendocrine Adrenal System

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A66-A67
Author(s):  
Audrey L Earnhardt ◽  
David G Riley ◽  
Noushin Ghaffari ◽  
Penny K Riggs ◽  
Charles R Long ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Clock Gene ◽  
Target Genes ◽  
Clock Genes ◽  
Expression Profiles ◽  
Primary Objective ◽  
Clock Gene Expression ◽  
Adrenal System ◽  
Circadian Clock Genes

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.

Expression of circadian clock genes in retinal dopaminergic cells

2007 ◽  
Vol 24 (4) ◽  
pp. 573-580 ◽  
Author(s):  
RONALD DORENBOS ◽  
MASSIMO CONTINI ◽  
HAJIME HIRASAWA ◽  
STEFANO GUSTINCICH ◽  
ELIO RAVIOLA
Keyword(s):  
Circadian Clock ◽  
Light Adaptation ◽  
Clock Genes ◽  
Negative Control ◽  
Circadian Oscillators ◽  
Interesting Candidate ◽  
Circadian Clock Genes ◽  
Core Components ◽  
A Site

The mammalian neural retina contains single or multiple intrinsic circadian oscillators that can be directly entrained by light cycles. Dopaminergic amacrine (DA) cells represent an especially interesting candidate as a site of the retinal oscillator because of the crucial role of dopamine in light adaptation, and the widespread distribution of dopamine receptors in the retina. We hereby show by single-cell, end-point RT-PCR that retinal DA cells contain the transcripts for six core components of the circadian clock: Bmal1, Clock, Cry1, Cry2, Per1, and Per2. Rod photoreceptors represented a negative control, because they did not appear to contain clock transcripts. We finally confirmed that DA cells contain the protein encoded by the Bmal1 gene by comparing immunostaining of the nuclei of DA cells in the retinas of wildtype and Bmal1−/− mice. It is therefore likely that DA cells contain a circadian clock that anticipates predictable variations in retinal illumination.

scholarly journals Identification and characterization of circadian clock genes in a native tobacco, Nicotiana attenuata

2012 ◽  
Vol 12 (1) ◽  
pp. 172 ◽  
Author(s):  
Felipe Yon ◽  
Pil-Joon Seo ◽  
Jae Ryu ◽  
Chung-Mo Park ◽  
Ian T Baldwin ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Nicotiana Attenuata ◽  
Circadian Clock Genes ◽  
Identification And Characterization

scholarly journals Isolation and Characterization of Circadian Clock Genes in the Biofuel Plant Pongamia (Millettia pinnata)

2014 ◽  
Vol 8 (2) ◽  
pp. 760-774 ◽  
Author(s):  
Harry P. Winarto ◽  
Lim Chee Liew ◽  
Peter M. Gresshoff ◽  
Paul T. Scott ◽  
Mohan B. Singh ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Isolation And Characterization ◽  
Millettia Pinnata ◽  
Circadian Clock Genes

scholarly journals Association of Circadian Clock Gene Expression with Glioma Tumor Microenvironment and Patient Survival

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 ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Clock Gene ◽  
Clock Genes ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Circadian Clock Gene ◽  
Clock Gene Expression ◽  
Mutational Status ◽  
Circadian Clock Genes

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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