A Constant Light-Genetic Screen Identifies KISMET as a Regulator of Circadian Photoresponses 英文参考文献.docVIP

AConstantLight-GeneticScreenIdentifiesKISMETasa RegulatorofCircadianPhotoresponses Raphae¨lleDubruille1,AlejandroMurad1,2¤,MichaelRosbash3,PatrickEmery1,2* 1DepartmentofNeurobiology,UniversityofMassachusettsMedicalSchool,Worcester,Massachusetts,UnitedStatesofAmerica,2PrograminNeuroscience,Universityof Massachusetts Medical School, Worcester, Massachusetts, United States of America, 3Howard Hughes Medical Institute, National Center for Behavioral Genetics and DepartmentofBiology,Waltham,Massachusetts,UnitedStatesofAmerica Abstract Circadianpacemakersareessentialtosynchronizeanimalphysiologyandbehaviorwiththeday:nightcycle.Theyareself- 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).Uponlightactivation,CRYbindstothepacemakerproteinTIMELESS(TIM)andtriggersitsproteasomaldegradation, thus resetting the circadian pacemaker. To understand further the CRY input pathway, we conducted a misexpression screenunderconstantlightbasedontheobservationthatflieswithadisruptionintheCRYinputpathwayremainrobustly rhythmicinsteadofbecomingbehaviorallyarrhythmic.Wereporttheidentificationofmorethan20potentialregulatorsof CRY-dependent light responses. We demonstrate that one of them, the chromatin-remodeling enzyme KISMET (KIS), is necessaryfornormalcircadianphotoresponses,butdoesnotaffectthecircadianpacemaker.KISgeneticallyinteractswith 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 synchronizationofcircadianrhythmswiththeday:nightcycle. Citation:DubruilleR,MuradA,RosbashM,EmeryP(2009)ACons