ArticleMolecular and cellular biology1999
PER and TIM inhibit the DNA binding activity of a Drosophila CLOCK-CYC/dBMAL1 heterodimer without disrupting formation of the heterodimer: a basis for circadian transcription.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
96 citing papers in PubMed, 241 citations in OpenAlex.
- Fat body CLOCK restrains innate immunity and maintains survival under dietary stress inbioRxiv : the preprint server for biology · 2026Article
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- Article
- miR-2940-1 is involved in the circadian regulation of oviposition in Aedes albopictus.Insect science · 2025Article
- The ubiquitin-proteasome system in circadian regulation.Frontiers in neuroscience · 2025Review
- A circadian clock regulates the blood-brain barrier across phylogeny.Vitamins and hormones · 2024Review
- Contribution of cryptochromes and photolyases for insect life under sunlight.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2023Article
- miR-277 regulates the phase of circadian activity-rest rhythm inFrontiers in physiology · 2023Article
- Effect of the Citrus Flavone Nobiletin on Circadian Rhythms and Metabolic Syndrome.Molecules (Basel, Switzerland) · 2022Review
- Death of a Protein: The Role of E3 Ubiquitin Ligases in Circadian Rhythms of Mice and Flies.International journal of molecular sciences · 2022Review
- Ubiquitin proteasome system in circadian rhythm and sleep homeostasis: Lessons from Drosophila.Genes to cells : devoted to molecular & cellular mechanisms · 2022Review
- Fluorescent Reporters for Studying Circadian Rhythms in Drosophila melanogaster.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Regulation of Heme Oxygenase and Its Cross-Talks with Apoptosis and Autophagy under Different Conditions inAntioxidants (Basel, Switzerland) · 2021Article
- Recent Progress in Non-motor Features of Parkinson's Disease with a Focus on Circadian Rhythm Dysregulation.Neuroscience bulletin · 2021Review
- The Circadian Clock in Lepidoptera.Frontiers in physiology · 2021Review
- Article
- Time after time: circadian clock regulation of intestinal stem cells.Cellular and molecular life sciences : CMLS · 2020Review
- Circadian and Genetic Modulation of Visually-Guided Navigation in Drosophila Larvae.Scientific reports · 2020Article
- Ataxin2 functions via CrebA to mediate Huntingtin toxicity in circadian clock neurons.PLoS genetics · 2019Article
- Analysing the evolutional and functional differentiation of four types of Daphnia magna cryptochrome in Drosophila circadian clock.Scientific reports · 2019Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Drosophila CLOCK (dCLOCK) and CYCLE (CYC) (also referred to as dBMAL1) proteins are members of the basic helix-loop-helix PAS (PER-ARNT-SIM) superfamily of transcription factors and are required for high-level expression of the circadian clock genes period (per) and timeless (tim). Several lines of evidence indicate that PER, TIM, or a PER-TIM heterodimer somehow inhibit the transcriptional activity of a putative dCLOCK-CYC complex, generating a negative-feedback loop that is a core element of the Drosophila circadian oscillator. In this report we show that PER and/or TIM inhibits the binding of a dCLOCK-CYC heterodimer to an E-box-containing DNA fragment that is present in the 5' nontranscribed region of per and acts as a circadian enhancer element. Surprisingly, inhibition of this DNA binding activity by PER, TIM, or both is not accompanied by disruption of the association between dCLOCK and CYC. The results suggest that the interaction of PER, TIM, or both with the dCLOCK-CYC heterodimer induces a conformational change or masks protein regions in the heterodimer, leading to a reduction in DNA binding activity. Together with other findings, our results strongly suggest that daily cycles in the association of PER and TIM with the dCLOCK-CYC complex probably contribute to rhythmic expression of per and tim.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.