Splice variants of DOMINO control Drosophila circadian behavior and pacemaker neuron maintenance

Autoři: Zhenxing Liu aff001;  Christine A. Tabuloc aff002;  Yongbo Xue aff001;  Yao Cai aff002;  Pearson Mcintire aff001;  Ye Niu aff001;  Vu H. Lam aff002;  Joanna C. Chiu aff002;  Yong Zhang aff001
Působiště autorů: Department of Biology, University of Nevada Reno, Reno, NV, United States of America aff001;  Department of Entomology and Nematology, University of California Davis, Davis, CA, United States of America aff002
Vyšlo v časopise: Splice variants of DOMINO control Drosophila circadian behavior and pacemaker neuron maintenance. PLoS Genet 15(10): e32767. doi:10.1371/journal.pgen.1008474
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008474


Circadian clocks control daily rhythms in behavior and physiology. In Drosophila, the small ventral lateral neurons (sLNvs) expressing PIGMENT DISPERSING FACTOR (PDF) are the master pacemaker neurons generating locomotor rhythms. Despite the importance of sLNvs and PDF in circadian behavior, little is known about factors that control sLNvs maintenance and PDF accumulation. Here, we identify the Drosophila SWI2/SNF2 protein DOMINO (DOM) as a key regulator of circadian behavior. Depletion of DOM in circadian neurons eliminates morning anticipatory activity under light dark cycle and impairs behavioral rhythmicity in constant darkness. Interestingly, the two major splice variants of DOM, DOM-A and DOM-B have distinct circadian functions. DOM-A depletion mainly leads to arrhythmic behavior, while DOM-B knockdown lengthens circadian period without affecting the circadian rhythmicity. Both DOM-A and DOM-B bind to the promoter regions of key pacemaker genes period and timeless, and regulate their protein expression. However, we identify that only DOM-A is required for the maintenance of sLNvs and transcription of pdf. Lastly, constitutive activation of PDF-receptor signaling rescued the arrhythmia and period lengthening of DOM downregulation. Taken together, our findings reveal that two splice variants of DOM play distinct roles in circadian rhythms through regulating abundance of pacemaker proteins and sLNvs maintenance.

Klíčová slova:

Circadian oscillators – Circadian rhythms – Drosophila melanogaster – Gene expression – Chronobiology – Neurons – Pacemakers – RNA interference


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