Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors
Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors
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DOI：
10.1177/0748730405277232
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发表时间：
2005-10-01
影响因子：
3.5
通讯作者：
Cermakian, N
中科院分区：
文献类型：
--
作者：
Guillaumond, F;Dardente, H;Cermakian, N
昼夜节律是由涉及时钟基因及其蛋白质产物的反馈回路产生的。在哺乳动物中，两个孤儿核受体REV-ERB α和ROR α在时钟基因Bmal1的转录中发挥重要作用。作者现在通过证明REV-ERB （α和β）和ROR （α， β和γ）家族的所有成员分别抑制和激活Bmal1转录，大大扩展了这些发现。作者进一步表明，Bmal1的转录是REV-ERBs和RORs在其特定反应元件（RORE）上竞争的结果。此外，他们证明Reverb基因在胸腺、骨骼肌和肾脏中表达相似，而Ror基因则表现出不同的表达模式。因此，结果表明REV-ERB和ROR家族的所有成员都是分子生物钟的重要组成部分。此外，它们在神经和外周组织中显著不同的表达模式为了解生物体内生物钟的功能差异提供了重要的见解。
Circadian rhythms result from feedback loops involving clock genes and their protein products. In mammals, 2 orphan nuclear receptors, REV-ERB alpha and ROR alpha, play important roles in the transcription of the clock gene Bmal1. The authors now considerably extend these findings with the demonstration that all members of the REV-ERB (alpha and beta) and ROR (alpha, beta, and gamma) families repress and activate Bmal1 transcription, respectively. The authors further show that transcription of Bmal1 is the result of competition between REV-ERBs and RORs at their specific response elements (RORE). Moreover, they demonstrate that Reverb genes are similarly expressed in the thymus, skeletal muscle, and kidney, whereas Ror genes present distinct expression patterns. Thus, the results indicate that all members of the REV-ERB and ROR families are crucial components of the molecular circadian clock. Furthermore, their strikingly different patterns of expression in nervous and peripheral tissues provide important insights into functional differences between circadian clocks within the organism.