The Drosophila 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 cyc, yet CYC expression is restricted to canonical clock cells despite evidence that cyc 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 Drosophila, reveal mechanisms governing circadian activator stability that are conserved in perhaps all eukaryotes, and suggest that Clk, cyc, and cry expression is sufficient to drive clock expression in naive cells.

中文翻译：

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CLOCK稳定CYCLE以启动果蝇中的时钟功能

在果蝇生物钟转录通过反馈回路保持时间。这些反馈环由CLOCK-CYCLE（CLK-CYC）异二聚体引发，该异二聚体激活了编码反馈抑制因子PERIOD和TIMELESS的基因的转录。昼夜节律钟通常在约150个大脑起搏器神经元以及头部和身体的许多外围组织中工作，但也可以通过在非钟表细胞中表达CLK来诱发。这些异位时钟也需要cyc，尽管有证据表明cyc，但CYC表达仅限于规范时钟细胞。mRNA被广泛表达。在这里，我们显示了CLK在体内的细胞培养和非时钟细胞中与CYC结合并使其稳定。异位时钟还需要蓝光感光体CRYPTOCHROME（CRY），这对于外围组织中的光夹带和时钟功能都是必需的。这些实验定义了启动果蝇昼夜节律功能所需的遗传结构，揭示了可能在所有真核生物中均守恒的昼夜节律活化剂稳定性的机制，并表明Clk，cyc和cry的表达足以驱动幼稚细胞中的时钟表达。