CREB influences timing and entrainment of the SCN circadian clock.
CREB influences timing and entrainment of the SCN circadian clock.
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DOI：
10.1177/0748730410381229
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发表时间：
2010-12
影响因子：
3.5
通讯作者：
Obrietan K
中科院分区：
文献类型：
--
作者：
Lee B;Li A;Hansen KF;Cao R;Yoon JH;Obrietan K
转录反馈回路是视交叉上核（SCN）昼夜节律（即24小时）时钟的核心，它与外部刺激信号（如光）以及在SCN系统范围内产生的节律性信号紧密耦合。CREB/CRE转录级联是将这些信号传递给分子钟的一个潜在信号通路。在这项研究中，我们使用了四环素诱导的CREB抑制小鼠品系，其中大约60%的SCN神经元表达转基因，来测试CREB在生物钟中的功能及其对明显节律的影响。我们发现，SCN中CREB信号的减弱导致光诱发时钟夹带的显著减少。对昼夜节律时间的检查显示，CREB抑制小鼠在没有外部光照提示的情况下表现出正常的自由运行节律。然而，在恒定光照条件下，通常会导致昼夜节律周期延长，CREB抑制小鼠表现出戏剧性的心律失常表型，这可以用强力霉素逆转。在细胞水平上，CREB的抑制导致生物钟蛋白PERIOD1和PERIOD2以及生物钟输出激素AVP和VIP的表达显著降低。总之，这些数据支持这样一种观点，即CRE转录途径协调转录事件，这些转录事件对于维持SCN时间和生物钟的光携带都是必不可少的。
The transcriptional feedback circuit, which is at the core of the suprachiasmatic nucleus (SCN) circadian (i.e., 24 h) clock, is tightly coupled to both external entrainment cues, such as light, as well as rhythmic cues that arise on a system-wide level within the SCN. One potential signaling pathway by which these cues are conveyed to the molecular clock is the CREB/CRE transcriptional cascade. In this study, we employed a tetracycline-inducible CREB repressor mouse strain, in which approximately 60% of the SCN neurons express the transgene, to test CREB functionality in the clock and its effects on overt rhythmicity. We show that attenuated CREB signaling in the SCN led to a significant reduction in light-evoked clock entrainment. An examination of circadian timing revealed that CREB repressor mice exhibited normal free-running rhythms in the absence of external lighting cues. However, under conditions of constant light, which typically leads to a lengthening of the circadian period, CREB repressor mice exhibited a dramatic arrhythmic phenotype, which could be reversed with doxycycline. At a cellular level, the repression of CREB led to a significant reduction in both the expression of the circadian clock proteins PERIOD1 and PERIOD2 and the clock output hormones AVP and VIP. Together, these data support the idea that the CRE transcriptional pathway orchestrates transcriptional events that are essential for both the maintenance of SCN timing and light entrainment of the circadian clock.
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影响因子：
4.7
作者：
Lee B;Cao R;Choi YS;Cho HY;Rhee AD;Hah CK;Hoyt KR;Obrietan K
通讯作者：
Obrietan K
影响因子：
6.1
作者：
Choi YS;Lee B;Cho HY;Reyes IB;Pu XA;Saido TC;Hoyt KR;Obrietan K
通讯作者：
Obrietan K
DOI：
10.1152/ajpregu.90463.2008
发表时间：
2009-03-01
影响因子：
2.8
作者：
Li, Jia-Da;Burton, Katherine J.;Zhou, Qun-Yong
通讯作者：
Zhou, Qun-Yong
影响因子：
6.1
作者：
Lee, Boyoung;Dziema, Heather;Obrietan, Karl
通讯作者：
Obrietan, Karl
影响因子：
5.3
作者：
Eide, EJ;Woolf, MF;Virshup, DM
通讯作者：
Virshup, DM