CRTC Potentiates Light-independent timeless Transcription to Sustain Circadian Rhythms in Drosophila.
CRTC Potentiates Light-independent timeless Transcription to Sustain Circadian Rhythms in Drosophila.
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CRTC 增强果蝇的光独立永恒转录以维持昼夜节律。
DOI：
10.1038/srep32113
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发表时间：
2016-08-31
影响因子：
4.6
通讯作者：
Lim C
中科院分区：
文献类型：
--
作者：
Kim M;Lee H;Hur JH;Choe J;Lim C
光是诱导内源性昼夜节律的最强环境时间线索之一。新出现的证据表明，CREB调节的转录辅激活因子1（CRTC 1）是这一途径中的关键参与者，刺激哺乳动物生物钟中光诱导的Period 1（Per 1）转录。在这里，我们证明了光独立的作用，果蝇CRTC在维持昼夜节律的行为。crtc基因座的基因组缺失导致在持续黑暗中长时间但差的运动节律。过表达或RNA干扰介导的昼夜节律起搏神经元中CRTC的耗竭同样会损害自由运行的行为节律，这意味着果蝇时钟对CRTC的剂量敏感。crtc无效突变延迟了昼夜节律基因表达的整体阶段，但它显着抑制时钟神经元中TIMELESS（TIM）蛋白的光独立振荡。事实上，CRTC过表达增强时钟/周期（CLK/CYC）激活的转录从tim，但不是每启动子在无时钟的S2细胞，而CRTC耗竭抑制it. Considerably，TIM过表达部分，但显着挽救crtc突变体的行为节律。综上所述，我们的数据表明，CRTC是一种新的共激活剂的CLK/CYC激活的TIM转录，以协调分子节奏与昼夜节律的行为超过24小时的时间尺度。因此，我们建议，CRTC依赖的时钟机制与不同物种之间的选择性时钟基因共同进化。
Light is one of the strongest environmental time cues for entraining endogenous circadian rhythms. Emerging evidence indicates that CREB-regulated transcription co-activator 1 (CRTC1) is a key player in this pathway, stimulating light-induced Period1 (Per1) transcription in mammalian clocks. Here, we demonstrate a light-independent role of Drosophila CRTC in sustaining circadian behaviors. Genomic deletion of the crtc locus causes long but poor locomotor rhythms in constant darkness. Overexpression or RNA interference-mediated depletion of CRTC in circadian pacemaker neurons similarly impairs the free-running behavioral rhythms, implying that Drosophila clocks are sensitive to the dosage of CRTC. The crtc null mutation delays the overall phase of circadian gene expression yet it remarkably dampens light-independent oscillations of TIMELESS (TIM) proteins in the clock neurons. In fact, CRTC overexpression enhances CLOCK/CYCLE (CLK/CYC)-activated transcription from tim but not per promoter in clock-less S2 cells whereas CRTC depletion suppresses it. Consistently, TIM overexpression partially but significantly rescues the behavioral rhythms in crtc mutants. Taken together, our data suggest that CRTC is a novel co-activator for the CLK/CYC-activated tim transcription to coordinate molecular rhythms with circadian behaviors over a 24-hour time-scale. We thus propose that CRTC-dependent clock mechanisms have co-evolved with selective clock genes among different species.
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DOI：
10.1038/nrm3072
发表时间：
2011-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.5
作者：
Beckwith, Esteban J.;Ceriani, M. Fernanda
通讯作者：
Ceriani, M. Fernanda
影响因子：
64.8
作者：
Grima, B;Chèlot, E;Rouyer, F
通讯作者：
Rouyer, F
影响因子：
3.7
作者：
DiAngelo, Justin R.;Erion, Renske;Sehgal, Amita
通讯作者：
Sehgal, Amita
影响因子：
18.2
作者：
Allada R;Chung BY
通讯作者：
Chung BY