scholarly journals Global Analysis of Circadian Expression in the Cyanobacterium Synechocystis sp. Strain PCC 6803

2005 ◽  
Vol 187 (6) ◽  
pp. 2190-2199 ◽  
Author(s):  
Ken-ichi Kucho ◽  
Kazuhisa Okamoto ◽  
Yuka Tsuchiya ◽  
Satoshi Nomura ◽  
Mamoru Nango ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Dna Microarrays ◽  
Global Analysis ◽  
Bacterial Species ◽  
Physiological State ◽  
Expression Patterns ◽  
Main Role ◽  
Circadian Expression ◽  
Pcc 6803

ABSTRACT Cyanobacteria are the only bacterial species found to have a circadian clock. We used DNA microarrays to examine circadian expression patterns in the cyanobacterium Synechocystis sp. strain PCC 6803. Our analysis identified 54 (2%) and 237 (9%) genes that exhibited circadian rhythms under stringent and relaxed filtering conditions, respectively. The expression of most cycling genes peaked around the time of transition from subjective day to night, suggesting that the main role of the circadian clock in Synechocystis is to adjust the physiological state of the cell to the upcoming night environment. There were several chromosomal regions where neighboring genes were expressed with similar circadian patterns. The physiological functions of the cycling genes were diverse and included a wide variety of metabolic pathways, membrane transport, and signal transduction. Genes involved in respiration and poly(3-hydroxyalkanoate) synthesis showed coordinated circadian expression, suggesting that the regulation is important for the supply of energy and carbon source in the night. Genes involved in transcription and translation also followed circadian cycling patterns. These genes may be important for output of the rhythmic information generated by the circadian clock. Our findings provided critical insights into the importance of the circadian clock on cellular physiology and the mechanism of clock-controlled gene regulation.

scholarly journals Phosphorylation of GAPVD1 Is Regulated by the PER Complex and Linked to GAPVD1 Degradation

2021 ◽  
Vol 22 (7) ◽  
pp. 3787
Author(s):  
Hussam Ibrahim ◽  
Philipp Reus ◽  
Anna Katharina Mundorf ◽  
Anna-Lena Grothoff ◽  
Valerie Rudenko ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Transcriptional Repression ◽  
Small Gtpase ◽  
Main Role ◽  
Interacting Proteins ◽  
Casein Kinase 1 ◽  
Bona Fide ◽  
Kinetics Of

Repressor protein period (PER) complexes play a central role in the molecular oscillator mechanism of the mammalian circadian clock. While the main role of nuclear PER complexes is transcriptional repression, much less is known about the functions of cytoplasmic PER complexes. We found with a biochemical screen for PER2-interacting proteins that the small GTPase regulator GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1), which has been identified previously as a component of cytoplasmic PER complexes in mice, is also a bona fide component of human PER complexes. We show that in situ GAPVD1 is closely associated with casein kinase 1 delta (CSNK1D), a kinase that regulates PER2 levels through a phosphoswitch mechanism, and that CSNK1D regulates the phosphorylation of GAPVD1. Moreover, phosphorylation determines the kinetics of GAPVD1 degradation and is controlled by PER2 and a C-terminal autoinhibitory domain in CSNK1D, indicating that the regulation of GAPVD1 phosphorylation is a novel function of cytoplasmic PER complexes and might be part of the oscillator mechanism or an output function of the circadian clock.

scholarly journals Bmal1 regulates circadian expression of cytochrome P450 3a11 and drug metabolism in mice

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Yanke Lin ◽  
Shuai Wang ◽  
Ziyue Zhou ◽  
Lianxia Guo ◽  
Fangjun Yu ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Drug Exposure ◽  
Defense Mechanism ◽  
Critical Role ◽  
The Body ◽  
Cellular Regulation ◽  
Circadian Expression ◽  
Distal Promoter ◽  
Daily Time

Abstract Metabolism is a major defense mechanism of the body against xenobiotic threats. Here we unravel a critical role of Bmal1 for circadian clock-controlled Cyp3a11 expression and xenobiotic metabolism. Bmal1 deficiency decreases the mRNA, protein and microsomal activity of Cyp3a11, and blunts their circadian rhythms in mice. A screen for Cyp3a11 regulators identifies two circadian genes Dbp and Hnf4α as potential regulatory mediators. Cell-based experiments confirm that Dbp and Hnf4α activate Cyp3a11 transcription by their binding to a D-box and a DR1 element in the Cyp3a11 promoter, respectively. Bmal1 binds to the P1 distal promoter to regulate Hnf4α transcriptionally. Cellular regulation of Cyp3a11 by Bmal1 is Dbp- and Hnf4α-dependent. Bmal1 deficiency sensitizes mice to toxicities of drugs such as aconitine and triptolide (and blunts circadian toxicity rhythmicities) due to elevated drug exposure. In summary, Bmal1 connects circadian clock and Cyp3a11 metabolism, thereby impacting drug detoxification as a function of daily time.

The Circadian Clock of the Unicellular Eukaryotic Model Organism Chlamydomonas reinhardtii

2003 ◽  
Vol 384 (5) ◽  
pp. 689-695 ◽  
Author(s):  
M. Mittag ◽  
V. Wagner
Keyword(s):  
Circadian Clock ◽  
Chlamydomonas Reinhardtii ◽  
Rna Binding ◽  
Outer Space ◽  
Expression Patterns ◽  
Model Organism ◽  
Nuclear Genome ◽  
Circadian System ◽  
Transcriptional Level ◽  
Circadian Expression

Abstract The green unicellular alga Chlamydomonas reinhardtii, also called 'green yeast', emerged in the past years as a model organism for specific scientific questions such as chloroplast biogenesis and function, the composition of the flagella including its basal apparatus, or the mechanism of the circadian clock. Sequencing of its chloroplast and mitochondrial genomes have already been completed and a first draft of its nuclear genome has also been released recently. In C. reinhardtii several circadian rhythms are physiologically well characterized, and one of them has even been shown to operate in outer space. Circadian expression patterns of nuclear and plastid genes have been studied. The mode of regulation of these genes occurs at the transcriptional level, although there is also evidence for posttranscriptional control. A clock-controlled, phylogenetically conserved RNA-binding protein was characterized in this alga, which interacts with several mRNAs that all contain a common cis-acting motif. Its function within the circadian system is currently under investigation. This review summarizes the current state of the knowledge about the circadian system in C. reinhardtii and points out its potential for future studies.

scholarly journals Estrogen-Responsive Genes Overlap with Triiodothyronine-Responsive Genes in a Breast Carcinoma Cell Line

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Nancy Bueno Figueiredo ◽  
Sílvia Helena Cestari ◽  
Sandro José Conde ◽  
Renata Azevedo Melo Luvizotto ◽  
Maria Teresa De Sibio ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Dna Microarrays ◽  
Expression Patterns ◽  
Breast Adenocarcinoma ◽  
Breast Carcinoma Cell Line ◽  
Expression Of Genes ◽  
Adenocarcinoma Cells ◽  
Pericentriolar Material ◽  
Mcf 7

It has been well established that estrogen plays an important role in the progression and treatment of breast cancer. However, the role of triiodothyronine (T3) remains controversial. We have previously shown its capacity to stimulate the development of positive estrogen receptor breast carcinoma, induce the expression of genes (PR, TGF-alpha) normally stimulated by estradiol (E2), and suppress genes (TGF-beta) normally inhibited by E2. Since T3regulates growth hormones, metabolism, and differentiation, it is important to verify its action on other genes normally induced by E2. Therefore, we used DNA microarrays to compare gene expression patterns in MCF-7 breast adenocarcinoma cells treated with E2and T3. Several genes were modulated by both E2and T3in MCF-7 cells (Student’st-test,P<0.05). Specifically, we found eight genes that were differentially expressed after treatment with both E2and T3, includingamphiregulin, fibulin 1, claudin 6, pericentriolar material 1, premature ovarian failure 1B, factor for adipocyte differentiation-104, sterile alpha motif domain containing 9, and likely ortholog of rat vacuole membrane protein 1(fold change > 2.0, pFDR < 0.05). We confirmed our microarray results by real-time PCR. Our findings reveal that certain genes in MCF-7 cells can be regulated by both E2and T3.

Circadian clock regulates hepatotoxicity of Tripterygium wilfordii through modulation of metabolism

2020 ◽  
Author(s):  
Huan Zhao ◽  
Yongbin Tong ◽  
Danyi Lu ◽  
Baojian Wu
Keyword(s):  
Circadian Clock ◽  
Diurnal Rhythm ◽  
Clock Gene ◽  
Plasma Concentrations ◽  
Systemic Exposure ◽  
Tripterygium Wilfordii ◽  
Circadian Expression ◽  
Circadian Time ◽  
Toxic Constituent

Abstract Objectives We aimed to determine the diurnal rhythm of Tripterygium wilfordii (TW) hepatotoxicity and to investigate a potential role of metabolism and pharmacokinetics in generating chronotoxicity. Methods Hepatotoxicity was determined based on assessment of liver injury after dosing mice with TW at different circadian time points. Circadian clock control of metabolism, pharmacokinetics and hepatotoxicity was investigated using Clock-deficient (Clock−/−) mice. Key findings Hepatotoxicity of TW displayed a significant circadian rhythm (the highest level of toxicity was observed at ZT2 and the lowest level at ZT14). Pharmacokinetic experiments showed that oral gavage of TW at ZT2 generated higher plasma concentrations (and systemic exposure) of triptolide (a toxic constituent) compared with ZT14 dosing. This was accompanied by reduced formation of triptolide metabolites at ZT2. Loss of Clock gene sensitized mice to TW-induced hepatotoxicity and abolished the time-dependency of toxicity that was well correlated with altered metabolism and pharmacokinetics of triptolide. Loss of Clock gene also decreased Cyp3a11 expression in mouse liver and blunted its diurnal rhythm. Conclusions Tripterygium wilfordii chronotoxicity was associated with diurnal variations in triptolide pharmacokinetics and circadian expression of hepatic Cyp3a11 regulated by circadian clock. Our findings may have implications for improving TW treatment outcome with a chronotherapeutic approach.

Prenatal programming of obesity in a swine model of leptin resistance: modulatory effects of controlled postnatal nutrition and exercise

2014 ◽  
Vol 5 (3) ◽  
pp. 248-258 ◽  
Author(s):  
A. Barbero ◽  
S. Astiz ◽  
C. Ovilo ◽  
C. J. Lopez-Bote ◽  
M. L. Perez-Solana ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Muscle Growth ◽  
Leptin Resistance ◽  
Control Group ◽  
Swine Model ◽  
Main Role ◽  
Prenatal Programming ◽  
Prenatal Malnutrition

The main role of early nutritional programming in the current rise of obesity and associated diseases is well known. However, translational studies are mostly based in postnatal food excess and, thus, there is a paucity of information on the phenotype of individuals with prenatal deficiencies but adequate postnatal conditions. Thus, we assessed the effects of prenatal programming (comparing descendants from females fed with a diet fulfilling 100 or only 50% of their nutritional requirements for pregnancy) on gene expression, patterns of growth and fattening, metabolic status and puberty attainment of a swine model of obesity/leptin resistance with controlled postnatal nutrition and opportunity of exercise. Maternal restriction was related to changes in the relationships among gene expression of positive (insulin-like growth factors 1 and 2) and negative (myostatin) regulators of muscle growth, with negative correlations in gilts from restricted pregnancies and positive relationships in the control group. In spite of these differences, the patterns of growth and fattening and the metabolic features during juvenile growth were similar in control gilts and gilts from restricted pregnancies. Concomitantly, there was a lack of differences in the timing of puberty attainment. However, after reaching puberty and adulthood, females from restricted pregnancies were heavier and more corpulent than control gilts, though such increases in weight and size were not accompanied by increases in adiposity. In conclusion, in spite of changes in gene expression induced by developmental programming, the propensity for higher weight and adiposity of individuals exposed to prenatal malnutrition may be modulated by controlled food intake and opportunity of physical exercise during infant and juvenile development.

The role of theSynechocystissp. PCC 6803 homolog of the circadian clock output regulator RpaA in day-night transitions

2018 ◽  
Vol 110 (5) ◽  
pp. 847-861 ◽  
Author(s):  
Christin Köbler ◽  
Siri-Jasmin Schultz ◽  
Dominik Kopp ◽  
Karsten Voigt ◽  
Annegret Wilde
Keyword(s):  
Circadian Clock ◽  
Circadian Clock Output ◽  
Pcc 6803

scholarly journals A Computational Analysis of Alternative Splicing across Mammalian Tissues Reveals Circadian and Ultradian Rhythms in Splicing Events

2019 ◽  
Vol 20 (16) ◽  
pp. 3977 ◽  
Author(s):  
Rukeia El-Athman ◽  
Dora Knezevic ◽  
Luise Fuhr ◽  
Angela Relógio
Keyword(s):  
Alternative Splicing ◽  
Circadian Clock ◽  
Computational Analysis ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Expression Patterns ◽  
Rna Seq ◽  
Ultradian Rhythms ◽  
Mammalian Tissues

Mounting evidence points to a role of the circadian clock in the temporal regulation of post-transcriptional processes in mammals, including alternative splicing (AS). In this study, we carried out a computational analysis of circadian and ultradian rhythms on the transcriptome level to characterise the landscape of rhythmic AS events in published datasets covering 76 tissues from mouse and olive baboon. Splicing-related genes with 24-h rhythmic expression patterns showed a bimodal distribution of peak phases across tissues and species, indicating that they might be controlled by the circadian clock. On the output level, we identified putative oscillating AS events in murine microarray data and pairs of differentially rhythmic splice isoforms of the same gene in baboon RNA-seq data that peaked at opposing times of the day and included oncogenes and tumour suppressors. We further explored these findings using a new circadian RNA-seq dataset of human colorectal cancer cell lines. Rhythmic isoform expression patterns differed between the primary tumour and the metastatic cell line and were associated with cancer-related biological processes, indicating a functional role of rhythmic AS that might be implicated in tumour progression. Our data shows that rhythmic AS events are widespread across mammalian tissues and might contribute to a temporal diversification of the proteome.

scholarly journals Homologs of Circadian Clock Proteins Impact the Metabolic Switch Between Light and Dark Growth in the Cyanobacterium Synechocystis sp. PCC 6803

2021 ◽  
Vol 12 ◽  
Author(s):  
Nina M. Scheurer ◽  
Yogeswari Rajarathinam ◽  
Stefan Timm ◽  
Christin Köbler ◽  
Joachim Kopka ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Response Regulator ◽  
Metabolic Switch ◽  
Carbon And Nitrogen ◽  
Clock Proteins ◽  
Genes Encoding ◽  
Carbon And Nitrogen Metabolism ◽  
Circadian Clock Proteins ◽  
Pcc 6803

The putative circadian clock system of the facultative heterotrophic cyanobacterial strain Synechocystis sp. PCC 6803 comprises the following three Kai-based systems: a KaiABC-based potential oscillator that is linked to the SasA-RpaA two-component output pathway and two additional KaiBC systems without a cognate KaiA component. Mutants lacking the genes encoding the KaiAB1C1 components or the response regulator RpaA show reduced growth in light/dark cycles and do not show heterotrophic growth in the dark. In the present study, the effect of these mutations on central metabolism was analyzed by targeted and non-targeted metabolite profiling. The strongest metabolic changes were observed in the dark in ΔrpaA and, to a lesser extent, in the ΔkaiAB1C1 mutant. These observations included the overaccumulation of 2-phosphoglycolate, which correlated with the overaccumulation of the RbcL subunit in the mutants, and taken together, these data suggest enhanced RubisCO activity in the dark. The imbalanced carbon metabolism in the ΔrpaA mutant extended to the pyruvate family of amino acids, which showed increased accumulation in the dark. Hence, the deletion of the response regulator rpaA had a more pronounced effect on metabolism than the deletion of the kai genes. The larger impact of the rpaA mutation is in agreement with previous transcriptomic analyses and likely relates to a KaiAB1C1-independent function as a transcription factor. Collectively, our data demonstrate an important role of homologs of clock proteins in Synechocystis for balanced carbon and nitrogen metabolism during light-to-dark transitions.

Sign in / Sign up

Export Citation Format

Share Document