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Artykuły w czasopismach na temat "CIRCADIAN CLOCK PROTEIN"

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Xiao, Yangbo, Ye Yuan, Mariana Jimenez, Neeraj Soni i Swathi Yadlapalli. "Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms". Proceedings of the National Academy of Sciences 118, nr 28 (7.07.2021): e2019756118. http://dx.doi.org/10.1073/pnas.2019756118.

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Circadian clocks regulate ∼24-h oscillations in gene expression, behavior, and physiology. While the genetic and molecular mechanisms of circadian rhythms are well characterized, what remains poorly understood are the intracellular dynamics of circadian clock components and how they affect circadian rhythms. Here, we elucidate how spatiotemporal organization and dynamics of core clock proteins and genes affect circadian rhythms in Drosophila clock neurons. Using high-resolution imaging and DNA-fluorescence in situ hybridization techniques, we demonstrate that Drosophila clock proteins (PERIOD and CLOCK) are organized into a few discrete foci at the nuclear envelope during the circadian repression phase and play an important role in the subnuclear localization of core clock genes to control circadian rhythms. Specifically, we show that core clock genes, period and timeless, are positioned close to the nuclear periphery by the PERIOD protein specifically during the repression phase, suggesting that subnuclear localization of core clock genes might play a key role in their rhythmic gene expression. Finally, we show that loss of Lamin B receptor, a nuclear envelope protein, leads to disruption of PER foci and per gene peripheral localization and results in circadian rhythm defects. These results demonstrate that clock proteins play a hitherto unexpected role in the subnuclear reorganization of core clock genes to control circadian rhythms, revealing how clocks function at the subcellular level. Our results further suggest that clock protein foci might regulate dynamic clustering and spatial reorganization of clock-regulated genes over the repression phase to control circadian rhythms in behavior and physiology.
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Lu, Renbin, Yufan Dong i Jia-Da Li. "Necdin regulates BMAL1 stability and circadian clock through SGT1-HSP90 chaperone machinery". Nucleic Acids Research 48, nr 14 (15.07.2020): 7944–57. http://dx.doi.org/10.1093/nar/gkaa601.

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Abstract Circadian clocks are endogenous oscillators that control ∼24-hour physiology and behaviors in virtually all organisms. The circadian oscillator comprises interconnected transcriptional and translational feedback loops, but also requires finely coordinated protein homeostasis including protein degradation and maturation. However, the mechanisms underlying the mammalian clock protein maturation is largely unknown. In this study, we demonstrate that necdin, one of the Prader-Willi syndrome (PWS)-causative genes, is highly expressed in the suprachiasmatic nuclei (SCN), the pacemaker of circadian clocks in mammals. Mice deficient in necdin show abnormal behaviors during an 8-hour advance jet-lag paradigm and disrupted clock gene expression in the liver. By using yeast two hybrid screening, we identified BMAL1, the core component of the circadian clock, and co-chaperone SGT1 as two necdin-interactive proteins. BMAL1 and SGT1 associated with the N-terminal and C-terminal fragments of necdin, respectively. Mechanistically, necdin enables SGT1-HSP90 chaperone machinery to stabilize BMAL1. Depletion of necdin or SGT1/HSP90 leads to degradation of BMAL1 through the ubiquitin–proteasome system, resulting in alterations in both clock gene expression and circadian rhythms. Taken together, our data identify the PWS-associated protein necdin as a novel regulator of the circadian clock, and further emphasize the critical roles of chaperone machinery in circadian clock regulation.
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Fu, Minnie, i Xiaoyong Yang. "The sweet tooth of the circadian clock". Biochemical Society Transactions 45, nr 4 (3.07.2017): 871–84. http://dx.doi.org/10.1042/bst20160183.

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The endogenous circadian clock is a key regulator of daily metabolic processes. On the other hand, circadian clocks in a broad range of tissues can be tuned by extrinsic and intrinsic metabolic cues. The bidirectional interaction between circadian clocks and metabolism involves both transcriptional and post-translational mechanisms. Nuclear receptors exemplify the transcriptional programs that couple molecular clocks to metabolism. The post-translational modifications of the core clock machinery are known to play a key role in metabolic entrainment of circadian clocks. O-linked N-acetylglucosamine modification (O-GlcNAcylation) of intracellular proteins is a key mediator of metabolic response to nutrient availability. This review highlights our current understanding of the role of protein O-GlcNAcylation in mediating metabolic input and output of the circadian clock.
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Mosier, Alexander E., i Jennifer M. Hurley. "Circadian Interactomics: How Research Into Protein-Protein Interactions Beyond the Core Clock Has Influenced the Model of Circadian Timekeeping". Journal of Biological Rhythms 36, nr 4 (31.05.2021): 315–28. http://dx.doi.org/10.1177/07487304211014622.

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The circadian clock is the broadly conserved, protein-based, timekeeping mechanism that synchronizes biology to the Earth’s 24-h light-dark cycle. Studies of the mechanisms of circadian timekeeping have placed great focus on the role that individual protein-protein interactions play in the creation of the timekeeping loop. However, research has shown that clock proteins most commonly act as part of large macromolecular protein complexes to facilitate circadian control over physiology. The formation of these complexes has led to the large-scale study of the proteins that comprise these complexes, termed here “circadian interactomics.” Circadian interactomic studies of the macromolecular protein complexes that comprise the circadian clock have uncovered many basic principles of circadian timekeeping as well as mechanisms of circadian control over cellular physiology. In this review, we examine the wealth of knowledge accumulated using circadian interactomics approaches to investigate the macromolecular complexes of the core circadian clock, including insights into the core mechanisms that impart circadian timing and the clock’s regulation of many physiological processes. We examine data acquired from the investigation of the macromolecular complexes centered on both the activating and repressing arm of the circadian clock and from many circadian model organisms.
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Fuchikawa, T., K. Beer, C. Linke-Winnebeck, R. Ben-David, A. Kotowoy, V. W. K. Tsang, G. R. Warman, E. C. Winnebeck, C. Helfrich-Förster i G. Bloch. "Neuronal circadian clock protein oscillations are similar in behaviourally rhythmic forager honeybees and in arrhythmic nurses". Open Biology 7, nr 6 (czerwiec 2017): 170047. http://dx.doi.org/10.1098/rsob.170047.

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Internal clocks driving rhythms of about a day (circadian) are ubiquitous in animals, allowing them to anticipate environmental changes. Genetic or environmental disturbances to circadian clocks or the rhythms they produce are commonly associated with illness, compromised performance or reduced survival. Nevertheless, some animals including Arctic mammals, open sea fish and social insects such as honeybees are active around-the-clock with no apparent ill effects. The mechanisms allowing this remarkable natural plasticity are unknown. We generated and validated a new and specific antibody against the clock protein PERIOD of the honeybee Apis mellifera (amPER) and used it to characterize the circadian network in the honeybee brain. We found many similarities to Drosophila melanogaster and other insects, suggesting common anatomical organization principles in the insect clock that have not been appreciated before. Time course analyses revealed strong daily oscillations in amPER levels in foragers, which show circadian rhythms, and also in nurses that do not, although the latter have attenuated oscillations in brain mRNA clock gene levels. The oscillations in nurses show that activity can be uncoupled from the circadian network and support the hypothesis that a ticking circadian clock is essential even in around-the-clock active animals in a constant physical environment.
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Zhang, Yang, Chunyan Duan, Jing Yang, Suping Chen, Qing Liu, Liang Zhou, Zhengyun Huang, Ying Xu i Guoqiang Xu. "Deubiquitinating enzyme USP9X regulates cellular clock function by modulating the ubiquitination and degradation of a core circadian protein BMAL1". Biochemical Journal 475, nr 8 (30.04.2018): 1507–22. http://dx.doi.org/10.1042/bcj20180005.

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Living organisms on the earth maintain a roughly 24 h circadian rhythm, which is regulated by circadian clock genes and their protein products. Post-translational modifications of core clock proteins could affect the circadian behavior. Although ubiquitination of core clock proteins was studied extensively, the reverse process, deubiquitination, has only begun to unfold and the role of this regulation on circadian function is not completely understood. Here, we use affinity purification and mass spectrometry analysis to identify probable ubiquitin carboxyl-terminal hydrolase FAF-X (USP9X) as an interacting protein of the core clock protein aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL or BMAL1). Through biochemical experiments, we discover that USP9X reduces BMAL1 ubiquitination, enhances its stability, and increases its protein level, leading to the elevated transcriptional activity. Bioluminescence measurement reveals that USP9X knockdown decreases the amplitude of the cellular circadian rhythm but the period and phase are not affected. Our experiments find a new regulator for circadian clock at the post-translational level and demonstrate a different regulatory function for the circadian clock through the deubiquitination and the up-regulation of the core clock protein BMAL1 in the positive limb of the transcription–translation feedback loop.
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Durgan, David J., Margaret A. Hotze, Tara M. Tomlin, Oluwaseun Egbejimi, Christophe Graveleau, E. Dale Abel, Chad A. Shaw, Molly S. Bray, Paul E. Hardin i Martin E. Young. "The intrinsic circadian clock within the cardiomyocyte". American Journal of Physiology-Heart and Circulatory Physiology 289, nr 4 (październik 2005): H1530—H1541. http://dx.doi.org/10.1152/ajpheart.00406.2005.

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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.
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Graf, Alexander, Diana Coman, R. Glen Uhrig, Sean Walsh, Anna Flis, Mark Stitt i Wilhelm Gruissem. "Parallel analysis of Arabidopsis circadian clock mutants reveals different scales of transcriptome and proteome regulation". Open Biology 7, nr 3 (marzec 2017): 160333. http://dx.doi.org/10.1098/rsob.160333.

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The circadian clock regulates physiological processes central to growth and survival. To date, most plant circadian clock studies have relied on diurnal transcriptome changes to elucidate molecular connections between the circadian clock and observable phenotypes in wild-type plants. Here, we have integrated RNA-sequencing and protein mass spectrometry data to comparatively analyse the lhycca1 , prr7prr9 , gi and toc1 circadian clock mutant rosette at the end of day and end of night. Each mutant affects specific sets of genes and proteins, suggesting that the circadian clock regulation is modular. Furthermore, each circadian clock mutant maintains its own dynamically fluctuating transcriptome and proteome profile specific to subcellular compartments. Most of the measured protein levels do not correlate with changes in their corresponding transcripts. Transcripts and proteins that have coordinated changes in abundance are enriched for carbohydrate- and cold-responsive genes. Transcriptome changes in all four circadian clock mutants also affect genes encoding starch degradation enzymes, transcription factors and protein kinases. The comprehensive transcriptome and proteome datasets demonstrate that future system-driven research of the circadian clock requires multi-level experimental approaches. Our work also shows that further work is needed to elucidate the roles of post-translational modifications and protein degradation in the regulation of clock-related processes.
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Clark, Amelia M., i Brian J. Altman. "Circadian control of macrophages in the tumor microenvironment." Journal of Immunology 208, nr 1_Supplement (1.05.2022): 165.06. http://dx.doi.org/10.4049/jimmunol.208.supp.165.06.

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Abstract Introduction All leukocytes tested to date have functional circadian clocks, and nearly every arm of the immune response is subject to circadian regulation. Circadian clocks instruct the time-of-day-dependent, rhythmic expression of genes in a tissue- and cell-specific manner. In macrophages (mΦs), the circadian clock regulates several factors that are critical to executing effective immune responses. Tumor-associated mΦs are major contributors to immune suppression in the tumor microenvironment (TME). Evidence suggests that metabolically stressful factors in the TME such as acidic pH and nutrient limitation promote mΦ-mediated immune suppression, and recent data point to dysregulation of the circadian clock downstream of metabolic stress. Methods We study the effect of TME-associated metabolic stress on the circadian clock of mΦs in vitro by culturing bone marrow-derived mΦs in conditions mimicking acidic pH and nutrient limitations that have been observed in the TME. To study the impact of mΦ-intrinsic circadian rhythms on tumorigenesis in vivo, we use mice genetically engineered to have a myeloid cell-specific disruption of the circadian clock via deletion of the key clock protein BMAL1. Results Oscillation of core clock proteins is altered in mΦs subjected to TME-associated metabolic stress. Additionally, we observe increased tumor growth in mice co-injected with mΦs whose circadian clocks were disrupted compared to mice co-injected with mΦs whose circadian clocks were functional. Conclusion Our data suggests that stressful conditions associated with the TME can alter the mΦ circadian clock, and that a functional circadian clock in mΦs can suppress tumor growth in a syngeneic murine tumor model of pancreatic cancer. This research has been supported by the following fellowships and grants: 2021-Current: Wilmot Predoctoral Cancer Research Fellowship, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 2020-2021: NIH T32 Training Grant in Cellular, Biochemical & Molecular Sciences, University of Rochester Medical Center, Rochester, NY
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Narumi, Ryohei, Yoshihiro Shimizu, Maki Ukai-Tadenuma, Koji L. Ode, Genki N. Kanda, Yuta Shinohara, Aya Sato, Katsuhiko Matsumoto i Hiroki R. Ueda. "Mass spectrometry-based absolute quantification reveals rhythmic variation of mouse circadian clock proteins". Proceedings of the National Academy of Sciences 113, nr 24 (31.05.2016): E3461—E3467. http://dx.doi.org/10.1073/pnas.1603799113.

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Absolute values of protein expression levels in cells are crucial information for understanding cellular biological systems. Precise quantification of proteins can be achieved by liquid chromatography (LC)–mass spectrometry (MS) analysis of enzymatic digests of proteins in the presence of isotope-labeled internal standards. Thus, development of a simple and easy way for the preparation of internal standards is advantageous for the analyses of multiple target proteins, which will allow systems-level studies. Here we describe a method, termed MS-based Quantification By isotope-labeled Cell-free products (MS-QBiC), which provides the simple and high-throughput preparation of internal standards by using a reconstituted cell-free protein synthesis system, and thereby facilitates both multiplexed and sensitive quantification of absolute amounts of target proteins. This method was applied to a systems-level dynamic analysis of mammalian circadian clock proteins, which consist of transcription factors and protein kinases that govern central and peripheral circadian clocks in mammals. Sixteen proteins from 20 selected circadian clock proteins were successfully quantified from mouse liver over a 24-h time series, and 14 proteins had circadian variations. Quantified values were applied to detect internal body time using a previously developed molecular timetable method. The analyses showed that single time-point data from wild-type mice can predict the endogenous state of the circadian clock, whereas data from clock mutant mice are not applicable because of the disappearance of circadian variation.
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Rozprawy doktorskie na temat "CIRCADIAN CLOCK PROTEIN"

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Chen, Weiwei. "Characterization of the movement of a circadian protein in the temperature-dependent root synchronization of Arabidopsis thaliana". Doctoral thesis, Universitat Autònoma de Barcelona, 2020. http://hdl.handle.net/10803/670449.

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El rellotge circadià està sincronitzat per senyals mediambientals externes, principalment la llum i la temperatura. Entendre com respon el rellotge circadià de la planta a les oscil·lacions de temperatura és crucial per comprendre la capacitat de resposta de la planta a l'entorn. En aquesta tesi doctoral, trobem una funció prevalent depenent de la temperatura de l'component de el rellotge d'Arabidopsis EARLY Flowering 4 (ELF4) en el rellotge circadià de l'arrel. En plantes en les quals l'àpex aeri s'ha eliminat, el rellotge pot funcionar en les arrels, tot i que exhibeix un període més curt i una fase avançada en comparació amb les arrels de plantes completes. Els assajos de microempelt mostren que ELF4 es mou des de l'àpex aeri per regular els ritmes en les arrels. El moviment de la proteïna ELF4 no transmet informació fotoperiòdica, sinó que és essencial per controlar el període de el rellotge circadià en l'arrel d'una manera depenent de la temperatura. Les baixes temperatures afavoreixen la mobilitat de ELF4, el que resulta en un rellotge de de ritme lent, mentre que les altes temperatures disminueixen el moviment, el que porta a un rellotge més ràpid. Per tant, el moviment de la proteïna ELF4 mòbil proporciona informació sobre la temperatura i ajuda a establir un diàleg entre l'àpex aeri i l'arrel de la planta per controlar el ritme circadià en l'arrel.
El reloj circadiano está sincronizado por señales medioambientales externas, principalmente la luz y la temperatura. Entender cómo responde el reloj circadiano de la planta a las oscilaciones de temperatura es crucial para comprender la capacidad de respuesta de la planta al medio ambiente. En esta Tesis Doctoral, encontramos una función prevalente dependiente de la temperatura del componente del reloj de Arabidopsis EARLY FLOWERING 4 (ELF4) en el reloj circadiano de la raíz. En plantas en las que el ápice aéreo se ha eliminado, el reloj puede funcionar correctamente en las raíces, aunque exhibe un período más corto y una fase avanzada en comparación con las raíces de plantas completas. Los ensayos de microinjerto muestran que ELF4 se mueve desde el ápice aéreo para regular los ritmos en las raíces. El movimiento de la proteína ELF4 no transmite información fotoperiódica, sino que es esencial para controlar el período del reloj circadiano en la raíz de una manera dependiente de la temperatura. Las bajas temperaturas favorecen la movilidad de ELF4, lo que resulta en un reloj de de ritmo lento, mientras que las altas temperaturas disminuyen el movimiento, lo que lleva a un reloj más rápido. Por lo tanto, el movimiento de la proteína ELF4 móvil proporciona información sobre la temperatura y ayuda a establecer un diálogo entre el ápice aéreo y la raíz de la planta para controlar el ritmo circadiano en la raíz.
The circadian clock is synchronized by external environment cues, mostly through light and temperature. Explaining how the plant circadian clock responds to temperature oscillations is crucial to understanding plant responsiveness to the environment. In this thesis, we found a prevalent temperature-dependent function of the Arabidopsis clock component EARLY FLOWERING 4 (ELF4) in the root clock. The clocks in roots are able to run properly in the absence of shoots although shoot excision leads to a shorter period and advanced phase in excised roots compared to entire roots. Micrografting assays show that ELF4 moves from shoots to regulate rhythms in roots. ELF4 movement does not convey photoperiodic information, but trafficking is essential for controlling the period of the root clock in a temperature-dependent manner. Low temperatures favour ELF4 mobility, resulting in a slow paced root clock, whereas high temperatures decrease movement, leading to a faster clock. Hence, the mobile ELF4 delivers temperature information and establishes a shoot-to-root dialogue that sets the pace of the clock in roots.
Universitat Autònoma de Barcelona. Programa de Doctorat en Biologia i Biotecnologia Vegetal
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Wallach, Thomas. "A dynamic circadian protein-protein interaction network". Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2012. http://dx.doi.org/10.18452/16604.

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Die dynamische Regulation von Protein-Protein Interaktionen (PPIs) ist wichtig für den Ablauf von biologischen Prozessen. Die circadiane Uhr, die einen ~24 Stunden Rhythmus generiert und eine Vielzahl von physiologischen Parametern steuert kann auch die Dynamik von PPIs regulieren. Um neue Erkenntnisse über regulatorische Mechanismen innerhalb des molekularen Oszillators zu gewinnen, habe ich zunächst alle möglichen PPIs zwischen 46 circadianen Komponenten mittels eines systematischen yeast-two-hybid (Y2H) Screens bestimmt. Dabei habe ich 109 bis dahin noch unbekannte PPIs identifiziert und einen repräsentativen Anteil mittels Co-Immunopräzipitationsexperimenten in humanen Zellen validiert. Unter den neuen PPIs habe ich bis dahin unbekannte Modulatoren der CLOCK/BMAL1 Transaktivierung identifiziert und dabei die Rolle der Proteinphosphatase 1 (PP1) als dynamischen Regulator der BMAL1 Stabilität funktionell charakterisiert. Das experimentelle PPI Netzwerk wurde mit bereits aus der Literatur bekannten PPIs und Interaktionspartnern ergänzt. Eine systematische RNAi Studie belegte außerdem die Relevanz der aus der Literatur stammenden Interaktoren für die ~24 Stunden Periodizität. Um eine Aussage über die Dynamik der PPIs im Netzwerk treffen zu können, wurden circadiane mRNA Expressionsdaten in das PPI Netzwerk integriert. Systematische Perturbationsstudien, in denen alle Komponenten des experimentellen Netzwerkes mittels RNAi herunterreguliert oder überexprimiert wurden, zeigten eine essentielle Bedeutung für die dynamischen PPIs innerhalb des circadianen Oszillators auf. Desweiteren wurden im circadianen PPI Netzwerk funktionelle Module identifiziert, welche dynamisch organsiert sind. Durch eine systemweite Analyse des humanen Proteoms wurden viele dynamische PPIs identifiziert, die biologische Prozesse wie z.B. Signaltransduktion und Zellzyklus miteinander verbinden. Rhythmische PPIs sind daher von Bedeutung für die zeitliche Organisation zellulärer Physiologie.
Essentially all biological processes depend on protein-protein interactions (PPIs). Timing of such interactions is crucial for regulatory function. Although circadian (~24 hrs) clocks constitute fundamental cellular timing mechanisms regulating important physiological processes PPI dynamics on this timescale are largely unknown. To elucidate so far unknown regulatory mechanisms within the circadian clockwork, I have systematically mapped PPIs among 46 circadian components using high-throughput yeast-two-hybrid (Y2H) interaction experiments. I have identified 109 so far uncharacterized interactions and successfully validated a sub-fraction via co-immunoprecipitation experiments in human cells. Among the novel PPIs, I have identified modulators of CLOCK/BMAL1 function and further characterized the role of protein phosphatase 1 (PP1) in the dynamic regulation of BMAL1 abundance. Furthermore, to generate a more comprehensive circadian PPI network, the experimental network was enriched and extended with additional interactions and interaction partners from literature, some of which turned out to be essential for normal circadian dynamics. The integration of circadian mRNA expression profiles allowed us to determine the interaction dynamics within our network. Systematic genetic perturbation studies (RNAi and overexpression in oscillating human cells) revealed a crucial role of dynamic regulation (via rhythmic PPIs) for the molecular clockwork. Furthermore, dynamic modular organization as a pervasive circadian network feature likely contributes to time-of-day dependent control of many cellular processes. Global analysis of the proteome regarding circadian regulation of biological processes via rhythmic PPIs revealed time-of-day dependent organization of the human interactome. Circadian PPIs dynamically connect many important cellular processes like signal transduction and cell cycle, which contribute to temporal organization of cellular physiology.
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Han, Linqu. "Molecular and genetic analysis of a novel F-box protein, ZEITLUPE, in the Arabidopsis circadian clock". Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1155569207.

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Geng, Ruishuang. "Characterization and functional analysis of ZEITLUPE protein in the regulation of the circadian clock and plant development". Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1149013919.

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Kunisue, Sumihiro. "Roles of the Orphan Receptor Gpr176-mediated G-protein Signaling in the Central Circadian Clock". Kyoto University, 2019. http://hdl.handle.net/2433/242672.

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Kim, Kevin Dae Keon. "The Translationally Controlled Tumor Protein (TCTP) associates to and destabilizes the Circadian Factor Period 2 (Per2)". Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/76848.

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Period 2 (Per2) is a core circadian factor responsible for its own negative regulation. It operates in the circadian clock, which affects multiple biological functions such as metabolic rate, hormone release, and core body temperature. The Per2 protein functions directly with factors in other biological functions such as tumor suppression, immune system, and metabolism. In many cases, the Per2 deficiency caused by disrupted expression is sufficient to create severe abnormalities in many of the mentioned functions. The sequence contains several domains and motifs in Per2 that are traditionally involved in protein interactions which suggests that Per2 serving a regulatory role by effecting downstream biological roles dependent on Per2 stability. In this work, we perform a two-hybrid screening assay using the C-terminal region of human Per2 and identified an extensive number of interactors. Utilizing a genetic ontology program, we assorted the list of clones into groups of proteins that are biologically relevant or operated in similar function. Through this program, we validated the two-hybrid screening by the clusters of biological function already attributed to hPer2 and identified new putative biological functions. We use the new putative interactors to gain further insight on the regulatory roles that hPer2 performs, in conjunction with operating as a core factor in circadian rhythmicity. We also show that Translationally Controlled Tumor Protein (TCTP) is capable of binding to hPer2 and is a novel interaction. When a sufficient amount of TCTP (1:1 molar stoichiometric ratio) is present in a system, a cleavage of hPer2 is observed in vitro. This cleavage occurs in reactions independent of ATP, ubiquitin, and the proteasome. The data points towards a method of cleavage similar to that of the archael lon-tk (Thermococcus kodakaraensis) that preferentially cleaved unstructured substrates in ATP-independent reactions.
Master of Science
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Han, Linqu. "Molecular and genetic analysis of a novel f-box protein, seitlupe, in the arabidopsis circadian clock". The Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1155569207.

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Butcher, Gregory Quinn. "The mitogen-activated protein kinase (MAPK) pathway a signaling conduit for photic entrainment of the central mammalian circadian clock /". Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1147206998.

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Kalive, Madhavi. "An investigation of complex formation by the Drosophila circadian clock protein double-time and the effects of the double-time[superscript s] mutation on complex formation". Morgantown, W. Va. : [West Virginia University Libraries], 1999. http://etd.wvu.edu/templates/showETD.cfm?recnum=886.

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Thesis (M.S.)--West Virginia University, 1999.
Title from document title page. Document formatted into pages; contains v, 65 p. : ill. (some col.) Vita. Includes abstract. Includes bibliographical references (p. [36]-45).
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Vakonakis, Ioannis. "Structure and function of circadian clock proteins and deuterium isotope effects in nucleic acid hydrogen bonds". Diss., Texas A&M University, 2003. http://hdl.handle.net/1969.1/2195.

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Circadian oscillators or clocks are a widespread, endogenous class of oscillatory mechanisms that control the ~24h temporal pattern of diverse organism functions. In cyanobacteria this mechanism is formed by three proteins, KaiA, KaiB and KaiC. KaiA is shown here to be a two domain protein that directly interacts with KaiC and enhances the KaiC autokinase activity. The amino-terminal domain of KaiA can be structurally categorized as a pseudo-receiver, a class of proteins used in signaling cascades and activated by direct protein??protein interactions. The carboxy-terminal domain interacts directly with KaiC, is sufficient to enhance the KaiC autokinase activity in a manner similar to full-length KaiA, and adopts a unique, all α-helical dimeric fold. The structure of this domain raises interesting probabilities regarding the mode of KaiA??KaiC interaction. The two KaiA domains are shown to directly interact with each other, which suggests a possible mechanism of signal transfer from the amino to carboxy-terminal domain. Hydrogen bonds are of paramount importance in nucleic acid structure and function. Here we show that changes in the width and anharmonicity of vibrational potential energy wells of hydrogen bonded groups can be measured in nucleic acids and can possibly be correlated to structural properties, such as length. Deuterium/protium fractionation factors, which are sensitive to the vibrational potential well width, were measured for the imino sites of thymidine residues involved in A:T base pairs or free in solution, and a correlation was established between decreasing fractionation factors and increasing imino proton chemical shift, δH3. Similarly, a correlation was observed between δH3and deuterium isotope effects (DIE) on chemical shift of thymidine carbon atoms. Combined these results indicate that as hydrogen-bond strength increases the vibrational potential wells of imino protons widen with a corresponding increase in anharmonicity. However, trans-hydrogen bond DIE on carbon chemical shifts of A:T base-paired adenosine residues do not correlate with those measured on thymidine residues. We propose that this lack of correlation is due to DIE dependence on base-pair geometry, which is not easily measured by traditional NMR experiments.
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Książki na temat "CIRCADIAN CLOCK PROTEIN"

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Low, Cher Heang (Shawn). Temperature compensation in the three-protein cyanobacterial circadian clock. 2010.

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Winter, Sherry Lynn. Genetic and functional characterization of the interaction of BRCA1 with the serine/threonine phosphatase, PP1, and the circadian clock proteins, Per1 and Per2. 2006.

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Części książek na temat "CIRCADIAN CLOCK PROTEIN"

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Ito-Miwa, Kumiko, Kazuki Terauchi i Takao Kondo. "Mechanism of the Cyanobacterial Circadian Clock Protein KaiC to Measure 24 Hours". W Circadian Rhythms in Bacteria and Microbiomes, 79–91. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-72158-9_5.

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Schweiger, H. G., R. Hartwig, G. Neuhaus, G. Neuhaus-Url, M. Li-Weber i M. Schweiger. "High Molecular Weight Protein is Presumably Essential for the Circadian Clock". W Temporal Order, 203–10. Berlin, Heidelberg: Springer Berlin Heidelberg, 1985. http://dx.doi.org/10.1007/978-3-642-70332-4_29.

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Sorkin, Maria L., i Dmitri A. Nusinow. "Using Tandem Affinity Purification to Identify Circadian Clock Protein Complexes from Arabidopsis". W Methods in Molecular Biology, 189–203. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1912-4_15.

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Kojima, Daisuke, i Yoshitaka Fukada. "Spectroscopic Analysis of Wavelength Sensitivities of Opsin-Type Photoreceptor Proteins". W Circadian Clocks, 169–85. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2577-4_8.

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Hogenesch, John B., i Steve A. Kay. "PAS Proteins in the Mammalian Circadian Clock". W PAS Proteins: Regulators and Sensors of Development and Physiology, 231–52. Boston, MA: Springer US, 2003. http://dx.doi.org/10.1007/978-1-4615-0515-0_10.

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Adams, Sally, i Isabelle A. Carré. "Chromatin Immunoprecipitation Protocol for Circadian Clock Proteins". W Methods in Molecular Biology, 135–50. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1912-4_12.

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Yoshitane, Hikari, i Yoshitaka Fukada. "Protein Modifications Pace the Circadian Oscillation of Biological Clocks". W Protein Modifications in Pathogenic Dysregulation of Signaling, 251–68. Tokyo: Springer Japan, 2015. http://dx.doi.org/10.1007/978-4-431-55561-2_16.

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Gul, Seref, i Ibrahim Halil Kavakli. "The Structure-Based Molecular-Docking Screen Against Core Clock Proteins to Identify Small Molecules to Modulate the Circadian Clock". W Methods in Molecular Biology, 15–34. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2249-0_2.

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Foster, Russell G., i Leon Kreitzman. "5. The tick-tock of the molecular clock". W Circadian Rhythms: A Very Short Introduction, 62–80. Oxford University Press, 2017. http://dx.doi.org/10.1093/actrade/9780198717683.003.0005.

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Circadian clocks in animals and plants arise from multiple and interconnected transcription–translation feedback loops that ensure the proper oscillation of thousands of genes in a tissue-specific manner. ‘The tick-tock of the molecular clock’ explains the transcription–translation feedback loop by describing the studies of circadian rhythms in Drosophila melanogaster, the fruit fly. The generation of a robust circadian rhythm entrained by the environment is achieved via multiple elements including the rate of transcription, translation, protein complex assembly, phosphorylation, other post-translation modification events, movement into the nucleus, transcriptional inhibition, and protein degradation. Similar mechanisms have been found in mammals, and insight is provided regarding research into how the mammalian molecular clock is entrained by light.
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Li, Yating, Haisen Zhang, Yiqun Wang, Dan Li i Huatao Chen. "Advances in circadian clock regulation of reproduction". W Advances in Protein Chemistry and Structural Biology. Elsevier, 2023. http://dx.doi.org/10.1016/bs.apcsb.2023.02.008.

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Streszczenia konferencji na temat "CIRCADIAN CLOCK PROTEIN"

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Cunningham, PS, HJ Durrington, RV Venkateswaran, M. Cypel, S. Keshavjee, JE Gibbs, AS Loudon, CW Chow, DW Ray i JF Blaikley. "S16 Circadian control of primary lung allograft dysfunction, mediated by the clock protein, reverbα". W British Thoracic Society Winter Meeting 2017, QEII Centre Broad Sanctuary Westminster London SW1P 3EE, 6 to 8 December 2017, Programme and Abstracts. BMJ Publishing Group Ltd and British Thoracic Society, 2017. http://dx.doi.org/10.1136/thoraxjnl-2017-210983.22.

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Fiser, Jaromir, Pavel Zitek i Jan Cerveny. "Relay Feedback Oscillator Design for Modeling Circadian Rhythms in Cyanobacteria". W ASME 2011 International Mechanical Engineering Congress and Exposition. ASMEDC, 2011. http://dx.doi.org/10.1115/imece2011-64996.

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The paper introduces a relay feedback oscillator for modeling circadian rhythms in cyanobacteria. The relay feedback oscillator is equipped with low pass filter F(jω), hysteresis-type relay and negative feedback. This negative feedback represents an autoregulatory mechanism of the circadian clock and the notion of this autoregulatory mechanism is based on the well-known Goodwin biochemical oscillator [1]. The relay is responsible for the mediation of both the activation and degradation of oscillator state variables (protein concentrations) and in this way the pacemaker is constituted. Later on, low pass filter poles are identified for the purpose of modeling auto-oscillations with the free running period of 24h and the method of the pole identification consists in an ultimate frequency test providing stability margin of a single-loop composed of the filter and the relay in the feedback. Next, a relay output / input ratio of amplitudes and hysteresis are found out by the graphical test of the single-loop on the stability margin which is carried out in Bode graph. Finally, the output correspondence of relay feedback oscillator model with Miyoshi oscillator [2] is provided because the Miyoshi oscillator is well recognized among biochemical oscillators for species of cyanobacteria.
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Kushibiki, Toshihiro, i Kunio Awazu. "A blue-violet laser irradiation stimulates bone nodule formation of mesenchymal stromal cells by the control of the circadian clock protein". W Biomedical Optics (BiOS) 2007, redaktorzy Steven L. Jacques i William P. Roach. SPIE, 2007. http://dx.doi.org/10.1117/12.699286.

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Adıgüzel, Dileyra. "Expression of circadian clock proteins during peri-implantation period in mice". W 15th International Congress of Histochemistry and Cytochemistry. Istanbul: LookUs Scientific, 2017. http://dx.doi.org/10.5505/2017ichc.pp-184.

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Raporty organizacyjne na temat "CIRCADIAN CLOCK PROTEIN"

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Casey, Therese, Sameer J. Mabjeesh, Avi Shamay i Karen Plaut. Photoperiod effects on milk production in goats: Are they mediated by the molecular clock in the mammary gland? United States Department of Agriculture, styczeń 2014. http://dx.doi.org/10.32747/2014.7598164.bard.

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US scientists, Dr. Theresa Casey and Dr. Karen Plaut, collaborated with Israeli scientists, Dr. SameerMabjeesh and Dr. AviShamay to conduct studies proposed in the BARD Project No. US-4715-14 Photoperiod effects on milk production in goats: Are they mediated by the molecular clock in the mammary gland over the last 3 years. CLOCK and BMAL1 are core components of the circadian clock and as heterodimers function as a transcription factor to drive circadian-rhythms of gene expression. Studies of CLOCK-mutant mice found impaired mammary development in late pregnancy was related to poor lactation performance post-partum. To gain a better understanding of role of clock in regulation of mammary development studies were conducted with the mammary epithelial cell line HC11. Decreasing CLOCK protein levels using shRNA resulted in increased mammary epithelial cell growth rate and impaired differentiation, with lower expression of differentiation markers including ad herens junction protein and fatty acid synthesis genes. When BMAL1 was knocked out using CRISPR-CAS mammary epithelial cells had greater growth rate, but reached stationary phase at a lower density, with FACS indicating cells were growing and dying at a faster rate. Beta-casein milk protein levels were significantly decreased in BMAL1 knockout cells. ChIP-seq analysis was conducted to identify BMAL1 target genes in mammary epithelial cells. Studies conducted in goats found that photoperiod duration and physiological state affected the dynamics of the mammary clock. Effects were likely independent of the photoperiod effects on prolactin levels. Interestingly, circadian rhythms of core body temperature, which functions as a key synchronizing cue sent out by the central clock in the hypothalamus, were profoundly affected by photoperiod and physiological state. Data support that the clock in the mammary gland regulates genes important to development of the gland and milk synthesis. We also found the clock in the mammary is responsive to changes in physiological state and photoperiod, and thus may serve as a mechanism to establish milk production levels in response to environmental cues.
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Wagner, D. Ry, Eliezer Lifschitz i Steve A. Kay. Molecular Genetic Analysis of Flowering in Arabidopsis and Tomato. United States Department of Agriculture, maj 2002. http://dx.doi.org/10.32747/2002.7585198.bard.

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The primary objectives for the US lab included: the characterization of ELF3 transcription and translation; the creation and characterization of various transgenic lines that misexpress ELF3; defining genetic pathways related to ELF3 function regulating floral initiation in Arabidopsis; and the identification of genes that either interact with or are regulated by ELF3. Light quality, photoperiod, and temperature often act as important and, for some species, essential environmental cues for the initiation of flowering. However, there is relatively little information on the molecular mechanisms that directly regulate the developmental pathway from the reception of the inductive light signals to the onset of flowering and the initiation of floral meristems. The ELF3 gene was identified as possibly having a role in light-mediated floral regulation since elj3 mutants not only flower early, but exhibit light-dependent circadian defects. We began investigating ELF3's role in light signalling and flowering by cloning the ELF3 gene. ELF3 is a novel gene only present in plant species; however, there is an ELF3 homolog within Arabidopsis. The Arabidopsis elj3 mutation causes arrhythmic circadian output in continuous light; however, we show conclusively normal circadian function with no alteration of period length in elj3 mutants in dark conditions and that the light-dependent arrhythmia observed in elj3 mutants is pleiotropic on multiple outputs regardless of phase. Plants overexpressing ELF3 have an increased period length in constant light and flower late in long-days; furthermore, etiolated ELF3-overexpressing seedlings exhibit a decreased acute CAB2 response after a red light pulse, whereas the null mutant is hypersensitive to acute induction. This finding suggests that ELF3 negatively regulates light input to both the clock and its outputs. To determine whether ELF3's action is phase dependent, we examined clock resetting by light pulses and constructed phase response curves. Absence of ELF3 activity causes a significant alteration of the phase response curve during the subjective night, and overexpression of ELF3 results in decreased sensitivity to the resetting stimulus, suggesting that ELF3 antagonizes light input to the clock during the night. Indeed, the ELF3 protein interacts with the photoreceptor PHYB in the yeast two-hybrid assay and in vitro. The phase ofELF3 function correlates with its peak expression levels of transcript and protein in the subjective night. ELF3 action, therefore, represents a mechanism by which the oscillator modulates light resetting. Furthermore, flowering time is dependent upon proper expression ofELF3. Scientifically, we've made a big leap in the understanding of the circadian system and how it is coupled so tightly with light reception in terms of period length and clock resetting. Agriculturally, understanding more about the way in which the clock perceives and relays temporal information to pathways such as those involved in the floral transition can lead to increased crop yields by enabling plants to be grown in suboptimal conditions.
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Johnson, Carl H. Cell-permeable Circadian Clock Proteins. Fort Belvoir, VA: Defense Technical Information Center, czerwiec 2002. http://dx.doi.org/10.21236/ada405529.

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Samach, Alon, Douglas Cook i Jaime Kigel. Molecular mechanisms of plant reproductive adaptation to aridity gradients. United States Department of Agriculture, styczeń 2008. http://dx.doi.org/10.32747/2008.7696513.bard.

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Annual plants have developed a range of different mechanisms to avoid flowering (exposure of reproductive organs to the environment) under adverse environmental conditions. Seasonal environmental events such as gradual changes in day length and temperature affect the timing of transition to flowering in many annual and perennial plants. Research in Arabidopsis and additional species suggest that some environmental signals converge on transcriptional regulation of common floral integrators such as FLOWERING LOCUS T (FT). Here we studied environmental induction of flowering in the model legume Medicago truncatula. Similarly to Arabidopsis, the transition to flowering in M. truncatula is hastened by long photoperiods and long periods of vernalization (4°C for 2-3 weeks). Ecotypes collected in Israel retain a vernalization response even though winter temperatures are way above 4°C. Here we show that this species is also highly responsive (flowers earlier) to mild ambient temperatures up to 19°C simulating winter conditions in its natural habitat. Physiological experiments allowed us to time the transition to flowering due to low temperatures, and to compare it to vernalization. We have made use of natural variation, and induced mutants to identify key genes involved in this process, and we provide here data suggesting that an FT gene in M.truncatula is transcriptionally regulated by different environmental cues. Flowering time was found to be correlated with MtFTA and MtFTB expression levels. Mutation in the MtFTA gene showed a late flowering phenotype, while over-expressing MtFTA in Arabidopsis complemented the ft- phenotype. We found that combination of 4°C and 12°C resulted in a synergistic increase in MtFTB expression, while combining 4°C and long photoperiods caused a synergistic increase in MtFTA expression. These results suggest that the two vernalization temperatures work through distinct mechanisms. The early flowering kalil mutant expressed higher levels of MtFTA and not MtFTB suggesting that the KALIL protein represses MtFTA specifically. The desert ecotype Sde Boker flowers earlier in response to short treatments of 8-12oc vernalization and expresses higher levels of MtFTA. This suggests a possible mechanism this desert ecotype developed to flower as fast as possible and finish its growth cycle before the dry period. MtFTA and FT expression are induced by common environmental cues in each species, and expression is repressed under short days. Replacing FT with the MtFTA gene (including regulatory elements) caused high MtFTA expression and early flowering under short days suggesting that the mechanism used to repress flowering under short days has diversified between the two species.The circadian regulated gene, GIGANTEA (GI) encodes a unique protein in Arabidopsis that is involved in flowering mechanism. In this research we characterized how the expression of the M.truncatula GI ortholog is regulated by light and temperature in comparison to its regulation in Arabidopsis. In Arabidopsis GI was found to be involved in temperature compensation to the clock. In addition, GI was found to be involved in mediating the effect of temperature on flowering time. We tested the influence of cold temperature on the MtGI gene in M.truncatula and found correlation between MtGI levels and extended periods of 12°C treatment. MtGI elevation that was found mostly after plants were removed from the cold influence preceded the induction of MtFT expression. This data suggests that MtGI might be involved in 12°C cold perception with respect to flowering in M.truncatula. GI seems to integrate diverse environmental inputs and translates them to the proper physiological and developmental outputs, acting through several different pathways. These research enabled to correlate between temperature and circadian clock in M.truncatula and achieved a better understanding of the flowering mechanism of this species.
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