Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm.
Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm.
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DOI：
10.1093/nar/gkt307
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发表时间：
2013-07
影响因子：
14.9
通讯作者：
Kim K
中科院分区：
文献类型：
--
作者：
Cheon S;Park N;Cho S;Kim K
糖皮质激素（GC）信号同步单个外周细胞的昼夜节律，并诱导昼夜节律基因的表达，包括Period1 （Per1）和Period2 （Per2）。然而，在Per2启动子区域没有GC响应元件（GRE）的报道。在这里，我们报道了GC信号诱导Per2的分子机制及其与昼夜节律调节的相关性。我们发现GC显著诱导Per2表达并延迟昼夜节律期。近端Per2启动子中重叠的GRE和E-box （GE2）区域负责gc介导的Per2诱导。Per2启动子中的GRE是独特的，因为脑和肌肉的arnt样蛋白-1 （BMAL1）对于gc诱导的Per2表达至关重要，而其他含有GRE的启动子，如Per1和小鼠乳腺肿瘤病毒，在缺乏BMAL1的情况下对地塞米松有反应。这种特殊的调节机制是由bmal1依赖的GC受体与Per2启动子中的GRE结合介导的。当Per2诱导被GRE或E-box突变取消时，与野生型相比，昼夜节律振荡期未能延迟。因此，目前的研究表明，GC介导的快速Per2诱导对于延缓昼夜节律至关重要。
Glucocorticoid (GC) signaling synchronizes the circadian rhythm of individual peripheral cells and induces the expression of circadian genes, including Period1 (Per1) and Period2 (Per2). However, no GC response element (GRE) has been reported in the Per2 promoter region. Here we report the molecular mechanisms of Per2 induction by GC signaling and its relevance to the regulation of circadian timing. We found that GC prominently induced Per2 expression and delayed the circadian phase. The overlapping GRE and E-box (GE2) region in the proximal Per2 promoter was responsible for GC-mediated Per2 induction. The GRE in the Per2 promoter was unique in that brain and muscle ARNT-like protein-1 (BMAL1) was essential for GC-induced Per2 expression, whereas other GRE-containing promoters, such as Per1 and mouse mammary tumor virus, responded to dexamethasone in the absence of BMAL1. This specialized regulatory mechanism was mediated by BMAL1-dependent binding of the GC receptor to GRE in Per2 promoter. When Per2 induction was abrogated by the mutation of the GRE or E-box, the circadian oscillation phase failed to be delayed compared with that of the wild-type. Therefore, the current study demonstrates that the rapid Per2 induction mediated by GC is crucial for delaying the circadian rhythm.
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影响因子：
4.8
作者：
Lee, Yongjin;Chen, Rongmin;Lee, Choogon
通讯作者：
Lee, Choogon
影响因子：
64.5
作者：
Balsalobre, A;Damiola, F;Schibler, U
通讯作者：
Schibler, U
影响因子：
56.9
作者：
Balsalobre, A;Brown, SA;Schibler, U
通讯作者：
Schibler, U
影响因子：
9.2
作者：
Balsalobre, A;Marcacci, L;Schibler, U
通讯作者：
Schibler, U
DOI：
10.1126/science.1222804
发表时间：
2012-07-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Huang N;Chelliah Y;Shan Y;Taylor CA;Yoo SH;Partch C;Green CB;Zhang H;Takahashi JS
通讯作者：
Takahashi JS