Light-Independent Role of CRY1 and CRY2 in the Mammalian Circadian Clock

Griffin, Edmund A.; Staknis, David; Weitz, Charles J.

doi:10.1126/science.286.5440.768

Cited by 582 publications

(456 citation statements)

References 32 publications

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“…Protein levels of PER and CRY are tightly regulated by stabilization and proteasome‐based degradation upon (de)phosphorylation 11, 12. After accumulation and dimerization of PER and CRY in the cytoplasm, they translocate to the nucleus in which they inhibit BMAL1:CLOCK‐mediated transcription 13 and therefore also their own transcription 14, 15, 16. Disturbing this molecular negative feedback loop results in an affected period or amplitude of circadian rhythmicity 5, 17.…”

Section: The Molecular Clock Comprises a Transcriptional/translationamentioning

confidence: 99%

Circadian clocks: from stem cells to tissue homeostasis and regeneration

2017

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The circadian clock is an evolutionarily conserved timekeeper that adapts body physiology to diurnal cycles of around 24 h by influencing a wide variety of processes such as sleep‐to‐wake transitions, feeding and fasting patterns, body temperature, and hormone regulation. The molecular clock machinery comprises a pathway that is driven by rhythmic docking of the transcription factors BMAL1 and CLOCK on clock‐controlled output genes, which results in tissue‐specific oscillatory gene expression programs. Genetic as well as environmental perturbation of the circadian clock has been implicated in various diseases ranging from sleep to metabolic disorders and cancer development. Here, we review the origination of circadian rhythms in stem cells and their function in differentiated cells and organs. We describe how clocks influence stem cell maintenance and organ physiology, as well as how rhythmicity affects lineage commitment, tissue regeneration, and aging.

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Section: The Molecular Clock Comprises a Transcriptional/translationamentioning

confidence: 99%

Circadian clocks: from stem cells to tissue homeostasis and regeneration

2017

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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.

144

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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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“…For instance, the expression of Per1 and Per2, two "clock" genes often used as state variables of the molecular circadian clock, is decreased in Clock mutant mice (Oishi et al, 2000;Ripperger et al, 2000) and increased in Cry1,2 Ϫ/Ϫ mice (Griffin et al, 1999;Okamura et al, 1999;Vitaterna et al, 1999). Even the sleep abnormalities in mice lacking Dbp might be associated with reduced Per expression because, at least in vitro, DBP can amplify the CLOCK:BMAL1-induced Per transcription (Yamaguchi et al, 2000).…”

Section: Conclusion Sleep Homeostasis As An Oscillatory Network Of Trmentioning

confidence: 99%

Perchance to dream: Solving the mystery of sleep through genetic analysis

Shaw

Franken

2002

J. Neurobiol.

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Sleep has been identified in all mammals and nonmammalian vertebrates that have been critically evaluated. In addition, sleep-like states have also been identified and described in several invertebrates. Despite this prevalence throughout the animal kingdom, the function of sleep remains a mystery. The completion of several genome sequencing projects has led to the expectation that fundamental aspects of sleep can be elucidated through genetic dissection. Indeed, studies in both the mouse and fly have begun to reveal tantalizing suggestions about the underlying principles that regulate sleep homeostasis. In this article we will review recent studies that have used genetic techniques to evaluate sleep in the fruit fly and the mouse.

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Light-Independent Role of CRY1 and CRY2 in the Mammalian Circadian Clock

Cited by 582 publications

References 32 publications

Circadian clocks: from stem cells to tissue homeostasis and regeneration

Circadian clocks: from stem cells to tissue homeostasis and regeneration

Circadian regulation of lipid metabolism

Perchance to dream: Solving the mystery of sleep through genetic analysis

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