Preitner Nicolas, Damiola Francesca, Lopez-Molina Luis, Zakany Joszef, Duboule Denis, Albrecht Urs, Schibler Ueli
Department of Molecular Biology, Sciences II, University of Geneva, 30, Quai Ernest Ansermet, CH 1211 -4, Geneva, Switzerland.
Cell. 2002 Jul 26;110(2):251-60. doi: 10.1016/s0092-8674(02)00825-5.
Mammalian circadian rhythms are generated by a feedback loop in which BMAL1 and CLOCK, players of the positive limb, activate transcription of the cryptochrome and period genes, components of the negative limb. Bmal1 and Per transcription cycles display nearly opposite phases and are thus governed by different mechanisms. Here, we identify the orphan nuclear receptor REV-ERBalpha as the major regulator of cyclic Bmal1 transcription. Circadian Rev-erbalpha expression is controlled by components of the general feedback loop. Thus, REV-ERBalpha constitutes a molecular link through which components of the negative limb drive antiphasic expression of components of the positive limb. While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation.
哺乳动物的昼夜节律由一个反馈回路产生,其中正向环节的参与者BMAL1和CLOCK激活负向环节的隐花色素基因和周期基因的转录。Bmal1和Per转录周期显示出几乎相反的相位,因此受不同机制调控。在这里,我们确定孤儿核受体REV-ERBα是循环Bmal1转录的主要调节因子。昼夜节律的Rev-erbalpha表达受一般反馈回路成分的控制。因此,REV-ERBα构成了一个分子联系,通过它负向环节的成分驱动正向环节的成分产生反相表达。虽然REV-ERBα影响周期长度并影响生物钟的相移特性,但它不是昼夜节律产生所必需的。