A new mammalian <i>period</i> gene predominantly expressed in the suprachiasmatic nucleus

Takumi, Toru; Matsubara, Chiaki; Shigeyoshi, Yasufumi; Taguchi, Kouji; Yagita, Kazuhiro; Maebayashi, Yoshiro; Sakakida, Yoko; Okumura, Katsuhiko; Takashima, Naoyuki; Okamura, Hitoshi

doi:10.1046/j.1365-2443.1998.00178.x

Cited by 222 publications

(167 citation statements)

References 25 publications

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“…5) in which the amplitude of the circadian pacemaker is reduced in Clock mutants, but the perturbing effects of resetting agents such as light or medium changes remain the same. Because Per1 and Per2 oscillate in the SCN in constant darkness and are rapidly induced by light during the subjective night, these two genes have been thought to represent the light-responsive elements of the mammalian circadian pacemaker at the molecular level (8)(9)(10)(11)(27)(28)(29)(30). In this model, we represent PER levels as a state variable in a simple 2D limit cycle oscillator shown diagrammatically in Fig.…”

Section: Discussionmentioning

confidence: 99%

The mouse Clock mutation reduces circadian pacemaker amplitude and enhances efficacy of resetting stimuli and phase–response curve amplitude

Vitaterna

Chang

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionmentioning

confidence: 99%

The mouse Clock mutation reduces circadian pacemaker amplitude and enhances efficacy of resetting stimuli and phase–response curve amplitude

Vitaterna

Chang

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

208

200

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“…31 This gene was literally cloned as a secondary mammalian period gene, after Per1. 32,33 However, it has been recently reported that Per1 is not absolutely required for the generation and maintenance of circadian rhythms, 34,35 while Per2 shows a robust cell-autonomous circadian fluctuation in its transcription, being a core component for rhythm generation. Perhaps the lack of correlation between Bmal1 and Per2 found in the visceral fat depot from the patients studied is related to the negative association of Per2 with abdominal fat accumulation.…”

Section: Discussionmentioning

confidence: 99%

Clock genes are implicated in the human metabolic syndrome

et al. 2007

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Background: Clock genes play a role in adipose tissue (AT) in animal experimental models. However, it remains to be elucidated whether these genes are expressed in human AT. Objective: We investigated the expression of several clock genes, Bmal1, Per2 and Cry1, in human AT from visceral and subcutaneous abdominal depots. A second objective was to elucidate whether these clock genes expressions were related to the metabolic syndrome features. Methods: Visceral and subcutaneous AT samples were obtained from morbid obese men (n ¼ 8), age: 42713 years and body mass indexX40 kg/m 2 , undergoing laparoscopic surgery due to obesity. Biopsies were taken as paired samples at the beginning of the surgical process (1100 hour). Metabolic syndrome features such as waist circumference, plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein (LDL) cholesterol were also studied. Homeostasis model assessment index of insulin resistance was also calculated. The expression of the different clock genes, hBmal1, hPer2 and hCry1, was determined by quantitative real-time PCR. Results: Clock genes were expressed in both human AT depots. hBmal1 expression was significantly lower than hPer2 and hCry1 in both AT (Po0.001). All genes were highly correlated to one another in the subcutaneous fat, while no correlation was found between Bmal1 and Per2 in the visceral AT. Clock genes AT expression was associated with the metabolic syndrome parameters: hPer2 expression level from visceral depot was inversely correlated to waist circumference (Po0.01), while the three clock genes studied were significantly and negatively correlated to total cholesterol and LDL cholesterol (Po0.01). Conclusion: We have demonstrated for the first time in humans that clock genes are expressed in both subcutaneous and visceral fat. Their association with abdominal fat content and cardiovascular risk factors may be an indicator of the potential role of these clock genes in the metabolic syndrome disturbances.

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“…Sequence analysis predicts the existence of a helix-loop-helix motive N-terminal to the PAS-A domain of mPER1, 2, and 3 (5,29,30) and secondary structure predictions suggest this N-terminal region to be mostly α-helical. To explore its potential contribution to homodimer formation, we have determined the dimer affinity of the N-terminally extended mPER3 PAS domain fragment mPER3 , which includes the predicted helix-loophelix motive (Fig.…”

Section: Analysis Of Mper Pas Domain Interactions In Solutionmentioning

confidence: 99%

Unwinding the differences of the mammalian PERIOD clock proteins from crystal structure to cellular function

Kucera

Schmalen

Hennig

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The three PERIOD homologues mPER1, mPER2, and mPER3 constitute central components of the mammalian circadian clock. They contain two PAS (PER-ARNT-SIM) domains (PAS-A and PAS-B), which mediate homo-and heterodimeric mPER-mPER interactions as well as interactions with transcription factors and kinases. Here we present crystal structures of PAS domain fragments of mPER1 and mPER3 and compare them with the previously reported mPER2 structure. The structures reveal homodimers, which are mediated by interactions of the PAS-B β-sheet surface including a highly conserved tryptophan (Trp448 mPER1 , Trp419 mPER2 , Trp359 mPER3 ). mPER1 homodimers are additionally stabilized by interactions between the PAS-A domains and mPER3 homodimers by an N-terminal region including a predicted helix-loop-helix motive. We have verified the existence of these homodimer interfaces in solution and inside cells using analytical gel filtration and luciferase complementation assays and quantified their contributions to homodimer stability by analytical ultracentrifugation. We also show by fluorescence recovery after photobleaching analyses that destabilization of the PAS-B/tryptophan dimer interface leads to a faster mobility of mPER2 containing complexes in human U2OS cells. Our study reveals structural and quantitative differences between the homodimeric interactions of the three mouse PERIOD homologues, which are likely to contribute to their distinct clock functions.circadian clock | PAS domains | PERIOD proteins | protein interactions

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A new mammalian period gene predominantly expressed in the suprachiasmatic nucleus

Cited by 222 publications

References 25 publications

The mouse Clock mutation reduces circadian pacemaker amplitude and enhances efficacy of resetting stimuli and phase–response curve amplitude

The mouse Clock mutation reduces circadian pacemaker amplitude and enhances efficacy of resetting stimuli and phase–response curve amplitude

Clock genes are implicated in the human metabolic syndrome

Unwinding the differences of the mammalian PERIOD clock proteins from crystal structure to cellular function

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