Role of the CLOCK protein in the mammalian circadian mechanism

被引:1621
作者
Gekakis, N
Staknis, D
Nguyen, HB
Davis, FC
Wilsbacher, LD
King, DP
Takahashi, JS
Weitz, CJ [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA
[2] Northeastern Univ, Dept Biol, Boston, MA 02115 USA
[3] Northwestern Univ, Dept Neurobiol & Physiol, Howard Hughes Med Inst, Evanston, IL 60208 USA
[4] Northwestern Univ, Natl Sci Fdn, Ctr Biol Timing, Evanston, IL 60208 USA
关键词
D O I
10.1126/science.280.5369.1564
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mouse Clock gene encodes a bHLH-PAS protein that regulates circadian rhythms and is related to transcription factors that act as heterodimers. Potential partners of CLOCK were isolated in a two-hybrid screen, and one, BMAL1, was coexpressed with CLOCK and PER1 at known circadian clock sites in brain and retina. CLOCK-BMAL1 heterodimers activated transcription from E-box elements, a type of transcription factor-binding site, found adjacent to the mouse per1 gene and from an identical E-box known to be important for per gene expression in Drosophila. Mutant CLOCK from the dominant-negative Clock allele and BMAL1 formed heterodimers that bound DNA but failed to activate transcription, Thus, CLOCK-BMAL1 heterodimers appear to drive the positive component of per transcriptional oscillations, which are thought to underlie circadian rhythmicity.
引用
收藏
页码:1564 / 1569
页数:6
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