Role of Cyclic mPer2 Expression in the Mammalian Cellular Clock
Role of Cyclic mPer2 Expression in the Mammalian Cellular Clock
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DOI：
10.1128/mcb.25.5.1912-1921.2005
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发表时间：
2005-03
影响因子：
5.3
通讯作者：
Yoshinobu Yamamoto;K. Yagita;H. Okamura
中科院分区：
文献类型：
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作者：
Yoshinobu Yamamoto;K. Yagita;H. Okamura
摘要为了探索mPer2在哺乳动物细胞生物钟中的昼夜节律振荡中的作用，我们建立了成纤维细胞系，其中mPer2的表达通过四环素可调控的启动子控制。我们发现mPer2 mRNA的组成性表达和过表达严重损害了血清休克诱导的周期性生物钟基因的表达。此外，在较低mPer2 mRNA表达的条件下，即使在组成性mPer2 mRNA表达中，这些细胞中的mPER2蛋白积累也显示出明显的昼夜节律振荡，这表明mPER2的蛋白循环是昼夜节律反馈回路振荡所必需的。由于内在时钟振荡系统驱动的基因表达的节奏在mPer2的循环表达的情况下迅速衰减，转录节奏有助于维持时钟振荡。
ABSTRACT To explore the role of mPer2 in the circadian oscillation in the mammalian cellular clock, we established fibroblast cell lines in which expression of mPer2 is controlled through a tetracycline-regulatable promoter. We revealed that constitutive expression and overexpression of mPer2 mRNA severely impair serum shock-induced cyclic circadian clock gene expression. Moreover, under conditions of lower mPer2 mRNA expression, mPER2 protein accumulation in these cells showed clear circadian oscillation even in constitutive mPer2 mRNA expression, suggesting that the protein cycling of mPER2 was required for oscillation of the circadian feedback loop. Since the rhythms of gene expression driven by the intrinsic clock oscillation system dampen rapidly in the absence of cyclic expression of mPer2, the transcriptional rhythm helps to sustain the clock oscillation.