Department of Biology, Texas A&M University, College Station, TX 77845-3258.
Center for Biological Clocks Research, Texas A&M University, College Station, TX 77845-3258.
Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):10972-10977. doi: 10.1073/pnas.1707143114. Epub 2017 Sep 25.
The circadian clock keeps time via transcriptional feedback loops. These feedback loops are initiated by CLOCK-CYCLE (CLK-CYC) heterodimers, which activate transcription of genes encoding the feedback repressors PERIOD and TIMELESS. Circadian clocks normally operate in ∼150 brain pacemaker neurons and in many peripheral tissues in the head and body, but can also be induced by expressing CLK in nonclock cells. These ectopic clocks also require , yet CYC expression is restricted to canonical clock cells despite evidence that mRNA is widely expressed. Here we show that CLK binds to and stabilizes CYC in cell culture and in nonclock cells in vivo. Ectopic clocks also require the blue light photoreceptor CRYPTOCHROME (CRY), which is required for both light entrainment and clock function in peripheral tissues. These experiments define the genetic architecture required to initiate circadian clock function in , reveal mechanisms governing circadian activator stability that are conserved in perhaps all eukaryotes, and suggest that , , and expression is sufficient to drive clock expression in naive cells.
生物钟通过转录反馈环来计时。这些反馈环是由 CLOCK-CYCLE（CLK-CYC）异二聚体启动的，它激活编码反馈抑制剂 PERIOD 和 TIMELESS 的基因转录。生物钟通常在大约 150 个脑起搏器神经元和头部和身体的许多外周组织中运作，但也可以通过在非生物钟细胞中表达 CLK 来诱导。这些异位时钟也需要 ，然而，尽管有证据表明 mRNA 广泛表达，但 CYC 的表达仅限于典型的时钟细胞。在这里，我们表明 CLK 在细胞培养物中和体内非生物钟细胞中结合并稳定 CYC。异位时钟还需要蓝光光感受器 CRYPTOCHROME（CRY），它是外周组织中光适应和时钟功能所必需的。这些实验定义了在 中启动生物钟功能所需的遗传结构，揭示了在可能所有真核生物中保守的生物钟激活剂稳定性的调控机制，并表明 、 和 的表达足以驱动幼稚细胞中的时钟表达。
