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A Constant Light-Genetic Screen Identifies KISMET as a Regulator of Circadian Photoresponses

机译:恒定的发光屏幕将KISMET识别为昼夜节律性光响应的调节剂。

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Circadian pacemakers are essential to synchronize animal physiology and behavior with the day∶night cycle. They are self-sustained, but the phase of their oscillations is determined by environmental cues, particularly light intensity and temperature cycles. In Drosophila, light is primarily detected by a dedicated blue-light photoreceptor: CRYPTOCHROME (CRY). Upon light activation, CRY binds to the pacemaker protein TIMELESS (TIM) and triggers its proteasomal degradation, thus resetting the circadian pacemaker. To understand further the CRY input pathway, we conducted a misexpression screen under constant light based on the observation that flies with a disruption in the CRY input pathway remain robustly rhythmic instead of becoming behaviorally arrhythmic. We report the identification of more than 20 potential regulators of CRY-dependent light responses. We demonstrate that one of them, the chromatin-remodeling enzyme KISMET (KIS), is necessary for normal circadian photoresponses, but does not affect the circadian pacemaker. KIS genetically interacts with CRY and functions in PDF-negative circadian neurons, which play an important role in circadian light responses. It also affects daily CRY-dependent TIM oscillations in a peripheral tissue: the eyes. We therefore conclude that KIS is a key transcriptional regulator of genes that function in the CRY signaling cascade, and thus it plays an important role in the synchronization of circadian rhythms with the day∶night cycle.
机译:昼夜节律起搏器对于使动物的生理和行为与昼夜周期保持同步至关重要。它们是自持的,但其振荡的相位取决于环境提示,尤其是光强度和温度循环。在果蝇中,主要通过专用的蓝光感光体:CRYPTOCHROME(CRY)检测光。光激活后,CRY与起搏器蛋白质TIMELESS(TIM)结合并触发其蛋白酶体降解,从而使生物钟起搏器复位。为了进一步了解CRY输入途径,我们基于观察到在CRY输入途径中受干扰的果蝇保持强劲的节律性而不是行为上的心律失常,在恒定的光线下进行了一个错误表达屏幕。我们报告鉴定了20多个潜在的依赖CRY的光反应调节剂。我们证明其中之一,染色质重塑酶KISMET(KIS),对于正常的昼夜节律性光反应是必需的,但不影响昼夜节律性起搏器。 KIS与CRY遗传相互作用,并在PDF阴性昼夜神经元中起作用,而后者在昼夜光反应中起重要作用。它还会影响周围组织(眼睛)中每天依赖CRY的TIM振荡。因此,我们得出结论,KIS是在CRY信号级联反应中起作用的基因的关键转录调节因子,因此在昼夜节律与昼夜周期的同步中起着重要作用。

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