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Role of cyclic mPer2 expression in the mammalian cellular clock
Yoshinobu Yamamoto1, Kazuhiro Yagita, Hitoshi Okamura
1Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Molecular and Cellular Biology
|February 17, 2005
Summary
The circadian clock
Area of Science:
- Chronobiology
- Molecular Biology
- Genetics
Background:
- The mammalian cellular clock relies on intricate molecular feedback loops.
- Circadian rhythms regulate numerous physiological processes.
- The role of specific clock components, like mPer2, is crucial for understanding clock function.
Purpose of the Study:
- To investigate the function of mPer2 in maintaining circadian oscillations within mammalian cells.
- To determine how mPer2 expression levels impact the cyclic nature of circadian clock genes.
Main Methods:
- Established tetracycline-regulatable fibroblast cell lines to control mPer2 expression.
- Analyzed serum shock-induced circadian gene expression under varying mPer2 levels.
- Monitored mPER2 protein accumulation for oscillatory patterns.
Main Results:
- Constitutive and overexpression of mPer2 mRNA significantly disrupted circadian clock gene expression.
- Circadian oscillation of mPER2 protein was observed even with constant mPer2 mRNA expression.
- Cyclic mPER2 protein accumulation is essential for the circadian feedback loop's oscillation.
Conclusions:
- Transcriptional regulation of mPer2 is vital for sustaining the mammalian cellular clock.
- mPER2 protein cycling is a key determinant for the robustness of circadian rhythms.
- Disruption of mPer2 rhythmicity leads to rapid dampening of clock gene expression rhythms.