ArticlePLoS genetics2016
CLOCKWORK ORANGE Enhances PERIOD Mediated Rhythms in Transcriptional Repression by Antagonizing E-box Binding by CLOCK-CYCLE.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 47 citations in OpenAlex.
- The Evolutionary Flexibility of the Drosophila Circadian Clock: Network Constraints or Adaptive Freedom?Genome biology and evolution · 2026Article
- Interplay between circadian and other transcription factors-Implications for cycling transcriptome reprogramming.FEBS letters · 2026Review
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- Alternative splicing ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
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- Alternative splicing ofbioRxiv : the preprint server for biology · 2024Article
- Steroid receptor coactivator TAIMAN is a new modulator of insect circadian clock.PLoS genetics · 2023Article
- CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters.PLoS genetics · 2023Article
- CLOCKWORK ORANGE promotes CLOCK-CYCLE activation via the putative Drosophila ortholog of CLOCK INTERACTING PROTEIN CIRCADIAN.Current biology : CB · 2021Article
- TIMEOR: a web-based tool to uncover temporal regulatory mechanisms from multi-omics data.Nucleic acids research · 2021Article
- Integration of Circadian Clock Information in theJournal of biological rhythms · 2021Review
- Circadian regulation of night feeding and daytime detoxification in a formidable Asian pest Spodoptera litura.Communications biology · 2021Article
- CK2 Inhibits TIMELESS Nuclear Export and Modulates CLOCK Transcriptional Activity to Regulate Circadian Rhythms.Current biology : CB · 2021Article
- The role of clockwork orange in the circadian clock of the cricket Gryllus bimaculatus.Zoological letters · 2020Article
- Proteomic analysis of Drosophila CLOCK complexes identifies rhythmic interactions with SAGA and Tip60 complex component NIPPED-A.Scientific reports · 2020Article
- Nipped-A regulates the Drosophila circadian clock via histone deubiquitination.The EMBO journal · 2020Article
- Model and Non-model Insects in Chronobiology.Frontiers in behavioral neuroscience · 2020Review
- Article
- Drosophila CrebB is a Substrate of the Nonsense-Mediated mRNA Decay Pathway that Sustains Circadian Behaviors.Molecules and cells · 2019Article
- O-GlcNAcylation of PERIOD regulates its interaction with CLOCK and timing of circadian transcriptional repression.PLoS genetics · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Drosophila circadian oscillator controls daily rhythms in physiology, metabolism and behavior via transcriptional feedback loops. CLOCK-CYCLE (CLK-CYC) heterodimers initiate feedback loop function by binding E-box elements to activate per and tim transcription. PER-TIM heterodimers then accumulate, bind CLK-CYC to inhibit transcription, and are ultimately degraded to enable the next round of transcription. The timing of transcriptional events in this feedback loop coincide with, and are controlled by, rhythms in CLK-CYC binding to E-boxes. PER rhythmically binds CLK-CYC to initiate transcriptional repression, and subsequently promotes the removal of CLK-CYC from E-boxes. However, little is known about the mechanism by which CLK-CYC is removed from DNA. Previous studies demonstrated that the transcription repressor CLOCKWORK ORANGE (CWO) contributes to core feedback loop function by repressing per and tim transcription in cultured S2 cells and in flies. Here we show that CWO rhythmically binds E-boxes upstream of core clock genes in a reciprocal manner to CLK, thereby promoting PER-dependent removal of CLK-CYC from E-boxes, and maintaining repression until PER is degraded and CLK-CYC displaces CWO from E-boxes to initiate transcription. These results suggest a model in which CWO co-represses CLK-CYC transcriptional activity in conjunction with PER by competing for E-box binding once CLK-CYC-PER complexes have formed. Given that CWO orthologs DEC1 and DEC2 also target E-boxes bound by CLOCK-BMAL1, a similar mechanism may operate in the mammalian clock.
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