Molecular mechanism of cell-autonomous circadian gene expression of Period2, a crucial regulator of the mammalian circadian clock
Molecular mechanism of cell-autonomous circadian gene expression of Period2, a crucial regulator of the mammalian circadian clock
复制标题
DOI：
10.1091/mbc.e05-05-0396
复制
发表时间：
2006-02-01
影响因子：
3.3
通讯作者：
Takumi, T
中科院分区：
文献类型：
--
作者：
Akashi, M;Ichise, T;Takumi, T
尽管Period 2（Per 2）的昼夜转录是昼夜节律产生的基础，但其分子机制仍不清楚。在这里，我们报告说，细胞自主的昼夜节律转录Per 2是由两个转录元件，一个节奏的产生和其他相位控制。前者包含驱动振荡的E-box样序列（CACGTT），并且昼夜节律转录因子与之位点特异性结合，而且这种非典型E-box的性质不同于经典的昼夜节律E-box。电流反馈回路模型主要基于周期1。我们的研究结果不仅提供了令人信服的证据支持这一模型，但也解释了一个一般的基本机制，以产生各种模式的细胞自主昼夜节律基因表达的相位和幅度。
Although circadian transcription of Period2 (Per2) is fundamental for the generation of circadian rhythm, the molecular mechanism remains unclear. Here we report that cell-autonomous circadian transcription of Per2 is driven by two transcriptional elements, one for rhythm generation and the other for phase control. The former contains the E-box-like sequence (CACGTT) that is sufficient and indispensable to drive oscillation, and indeed circadian transcription factors site-specifically bind to it. Furthermore, the nature of this atypical E-box is different from that of the classical circadian E-box. The current feedback loop model is based mainly on Period1. Our results provide not only compelling evidence in support of this model but also an explanation for a general basic mechanism to produce various patterns in the phase and amplitude of cell-autonomous circadian gene expression.