Feedback repression is required for mammalian circadian clock function

Sato, Trey K.; Yamada, Rikuhiro G.; Ukai, Hideki; Baggs, Julie E.; Miraglia, Loren; Kobayashi, Tetsuya; Welsh, David K.; Kay, Steve A.; Ueda, Hiroki R.; Hogenesch, John B.

doi:10.1038/ng1745

Cited by 335 publications

(317 citation statements)

References 32 publications

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“…The BMAL1:CLOCK/NPAS2 transcriptional complex activates expression of Period (Per1 and Per2) and Cryptochrome (Cry1 and Cry2) genes by binding to E-box sequences in the promoter region (29)(30)(31) . The PER and CRY proteins accumulate in the cytoplasm, and then translocate to the nucleus in the evening to repress their own transcription by interacting with the BMAL1:CLOCK/NPAS2 complex (32)(33)(34)(35) . Hence, PER and CRY levels are higher during the day and lower at night, similar to the SCN neural activity rhythm.…”

Section: Regulation Of Clock-controlled Genes Involved In Lipid Metabmentioning

confidence: 99%

Circadian regulation of lipid metabolism

Gooley

2016

Proc. Nutr. Soc.

130

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The circadian system temporally coordinates daily rhythms in feeding behaviour and energy metabolism. The objective of the present paper is to review the mechanisms that underlie circadian regulation of lipid metabolic pathways. Circadian rhythms in behaviour and physiology are generated by master clock neurons in the suprachiasmatic nucleus (SCN). The SCN and its efferent targets in the hypothalamus integrate light and feeding signals to entrain behavioural rhythms as well as clock cells located in peripheral tissues, including the liver, adipose tissue and muscle. Circadian rhythms in gene expression are regulated at the cellular level by a molecular clock comprising a core set of clock genes/proteins. In peripheral tissues, hundreds of genes involved in lipid biosynthesis and fatty acid oxidation are rhythmically activated and repressed by clock proteins, hence providing a direct mechanism for circadian regulation of lipids. Disruption of clock gene function results in abnormal metabolic phenotypes and impaired lipid absorption, demonstrating that the circadian system is essential for normal energy metabolism. The composition and timing of meals influence diurnal regulation of metabolic pathways, with food intake during the usual rest phase associated with dysregulation of lipid metabolism. Recent studies using metabolomics and lipidomics platforms have shown that hundreds of lipid species are circadian-regulated in human plasma, including but not limited to fatty acids, TAG, glycerophospholipids, sterol lipids and sphingolipids. In future work, these lipid profiling approaches can be used to understand better the interaction between diet, mealtimes and circadian rhythms on lipid metabolism and risk for obesity and metabolic diseases.

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Section: Regulation Of Clock-controlled Genes Involved In Lipid Metabmentioning

confidence: 99%

Circadian regulation of lipid metabolism

Gooley

2016

Proc. Nutr. Soc.

130

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“…In this study, we collaborated with Dr. John B. Hogenesch's and Dr. Steve A. Kay's groups to change the molecular parameter for feedback repression by functional genomics and then tested the cellular phenotype caused by this parameter change by our in cellulo cycling assay system. Through this study, we have demonstrated the necessity of transcriptional repression for circadian clock function (Sato et al 2006).…”

Section: Analysis Of Clocksmentioning

confidence: 99%

“…However, direct evidence for the requirement of CRY-mediated repression of CLOCK/BMAL1 transcriptional activity in the maintenance of circadian clock function has yet to be presented. Here, in a fruitful collaboration with the J.B. Hogenesch and the S.A. Kay groups, we have successfully shown that feedback repression is actually required for mammalian circadian clock function (Sato et al 2006). To determine the requirement of feedback repression in circadian clock function, we sought to identify the CLOCK alleles that were insensitive to CRY1 repression but maintained normal transcriptional activity.…”

Section: Analysis Of Clocksmentioning

confidence: 99%

“…For each of these processes, we have been able to report several strategies and technologies as well as their application to specific questions in mammalian circadian clocks. This has included the identification of clock-controlled genes, clock-controlled cis elements, and clock transcriptional circuits driven by functional genomics (Ueda et al 2002c(Ueda et al , 2005 in system identification, parameter change of clock components by quantitative measurement (Sato et al 2006) in system analysis, dynamic and quantitative perturbation of clock and its application to one of the fundamental but yetunsolved questions, and singularity behavior of clocks (Ukai et al 2007) in system control. As for the effort of system design, we recently initiated our current project on in cellulo and in vitro reconstruction of mammalian circadian circuits.…”

Section: Hr Uedamentioning

confidence: 99%

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Systems Biology of Mammalian Circadian Clocks

Ueda¹

2007

Cold Spring Harbor Symposia on Quantitative Biology

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Recent large-scale efforts in genome sequencing, expression profiling, and functional screening have produced an embarrassment of riches for life science researchers, and biological data can now be accessed in quantities that are orders of magnitude greater than were available even a few years ago. The growing need for interpretation of data sets, as well as the accelerating demand for their integration to a higher-level understanding of life, has set the stage for the advent of systems biology (Kitano 2002a,b), in which biological processes and phenomena are approached as complex and dynamic systems. Systems biology is a natural extension of molecular biology and can be defined as "biology after identification of key gene(s)." We see systems-biological research as a multistage process, beginning with the comprehensive identification and quantitative analysis of individual system components and their networked interactions and leading to the ability to control existing systems toward the desired state and design new ones based on an understanding of structure and underlying dynamical principles (Fig. 1). Mammalian Circadian Clock as a Model SystemWe have taken the mammalian circadian clock as an initial model system that exhibits system-level dynamical and structural properties in order to develop research strategies and technologies for studies of complex and dynamic biological systems. The mammalian circadian clock consists of complexly integrated feedback and feedforward loops (Reppert and Weaver 2002) and also exhibits well-defined dynamical properties (Dunlap et al. 2004), including (1) endogenous oscillations of an approximately 24-hour period, (2) entrainment to external environmental changes (temperature and light cycle), (3) temperature-compensation over a wide range of temperature, and (4) synchronization of multiple cellular clocks despite the inevitable molecular noise. All of these dynamical properties would be difficult to elucidate without utilizing such system-level approaches. In addition to its advantage as a basic model system for systems-biological research, the function of the circadian clock is intimately involved in the control of metabolic and physiological processes (Panda et al. 2002;Reppert and Weaver 2002), and its dysregulation is associated with the onset and development of numerous human diseases, including sleep disorders, depression, and dementia. An improved understanding at the systems level promises to provide biomedical and clinical investigators with a powerful new arsenal for attacking these conditions. Development of Systems-Biological Approaches and Their Application to ClocksAttempts to elucidate the design principles of complex and dynamic biological systems such as the mammalian circadian clock may require (1) identification of wholenetwork structure through comprehensive (genome-wide) screening (system identification), (2) prediction and validation to derive the design principle through the accurate measurement of network behaviors (system analysis), (3) repair and co...

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“…Крім того, для циркадіальних факторів у ссавців ха рак терне явище зворотного зв'язку в механізмах регуляції: казеїнкіназа 1ε зв'язу ється з Per2, а потім з Cry та комплексом Clock:BMal1, створюючи негативну ре гуля торну петлю [10,13,14].…”

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Disturbance of the expression of circadian genes Per1, Clock and BMal1 in rat liver, lung, testis, kidney and heart under silver nanoparticles action on organism

et al. 2010

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Перебіг більшості фізіологічних і біохімічних процесів в організмі має циркаді-альний характер, а порушення механізмів їхньої регуляції є одною із причин виник-нення багатьох патологічних процесів, у тому числі й утворення злоякісних пухлин. У даній роботі дослідили вплив наночасток срібла на рівень експресії найбільш важливих генів, що регулюють перебіг в організмі циркадіальних процесів: Per1, Clock і BMal1, білкові продукти яких є компонентами циркадіального годинника. Одержані дані показали, що під впливом наночасток срібла зростає рівень експре-сії Per1 у печінці та легені і пригнічується у сім'янику. Рівень експресії мРНК Clock також посилюється у печінці та легені під впливом наночасток срібла, а пригнічу-ється у нирці. У той же час, у сім'янику та серці пригнічення експресії мРНК Clock виявлено лише на більш пізніх термінах дії наночасток срібла. Таким чином, при дії на організм наночасток срібла порушується експресія генів Per1, Clock та BMal1 у різних органах щурів. Це може спричинювати розлади у функціонуванні сигналь-них каскадів у клітинах і сприяти розвитку патологічних станів. Вплив наночасток срібла на ключові механізми регуляції метаболічних процесів у клітинах на рівні експресії ряду циркадіальних генів може слугувати важливим чутливим показни-ком дії на організм наночасток срібла.Ключові слова: Per1, Clock, BMal1, наночастки срібла, печінка, легеня, сім'я ник, щур.Поведінка більшості живих організмів, як і перебіг у них фізіологічних і біохіміч-них процесів, автономно коливаються з періодом, близьким до 24 год. Ці коливан-ня пов'язані зі зміною дня та ночі й називаються циркадіальними ритмами, а гене-руються вони у гіпоталамусі на молекулярному рівні так званим циркадіальним го-динником, причому більшість основних фізіологічних і метаболічних процесів в ор-ганізмі має циклічний характер [1][2][3][4]. Контролюються вони циркадіальними генами (Per1, Per2, Per3, Cry1, Cry2, Сlоск та BMal1), які кодують синтез важливих регуля-Biol.

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Feedback repression is required for mammalian circadian clock function

Cited by 335 publications

References 32 publications

Circadian regulation of lipid metabolism

Circadian regulation of lipid metabolism

Systems Biology of Mammalian Circadian Clocks

Disturbance of the expression of circadian genes Per1, Clock and BMal1 in rat liver, lung, testis, kidney and heart under silver nanoparticles action on organism

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