ArticleProceedings of the National Academy of Sciences of the United States of America2021
Molecular mechanism of the repressive phase of the mammalian circadian clock.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 176 citations in OpenAlex.
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- D-Box Binding Protein (DBP) as a Circadian Output Regulator: Molecular Mechanisms, Tissue-Specific Functions, and Disease Relevance.International journal of molecular sciences · 2026Review
- Nuclear CK1δ as a critical determinant of PER:CRY complex dynamics and circadian period.eLife · 2026Article
- Circadian clock control of breast cancer hallmarks: molecular mechanisms and therapeutic implications.Cancer metastasis reviews · 2026Review
- NADAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Circadian Controlled Transcription in Brain and Peripheral Organs of Juvenile and Adult Mice.International journal of molecular sciences · 2026Article
- Vitamin D as a Regulator of the Biological Clock-Implications for Circadian-Metabolic Dysregulation.International journal of molecular sciences · 2026Review
- Impact of E-Cigarette Use on Circadian Proteins and Cardiovascular Risk Markers.Journal of cardiovascular translational research · 2026Article
- Time after time - circadian clocks through the lens of oscillator theory.FEBS letters · 2026Review
- Biochemical mechanism of the mammalian circadian clock.FEBS letters · 2026Review
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A daily cycle of White Collar Complex dephosphorylation sustains circadian rhythmicity inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- AProceedings of the National Academy of Sciences of the United States of America · 2026Article
- HIV disrupts the lung molecular clock, leading to lung inflammation and features of emphysema.Communications biology · 2026Article
- Circadian regulation of osteoclast lysosomal-resorption machinery: implications for osteoporosis therapy.Frontiers in cell and developmental biology · 2026Review
- Temporal dynamics and functional annotation of transcriptome rhythmicity in HEK293T cells.PloS one · 2026Article
- The sleep-wake history contributes to rhythmic BMAL1 chromatin binding in the cerebral cortex but not in the liver.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- How cells tame noise while maintaining ultrasensitive transcriptional responses.PLoS computational biology · 2025Article
- Tuned by time: the role of circadian rhythms in metabolic energy sensing and chronotherapy.Annals of medicine · 2025Review
- Promoter Frame Position Affects Strength and Nature of Circadian Oscillations inInternational journal of molecular sciences · 2025Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The mammalian circadian clock consists of a transcription-translation feedback loop (TTFL) composed of CLOCK-BMAL1 transcriptional activators and CRY-PER transcriptional repressors. Previous work showed that CRY inhibits CLOCK-BMAL1-activated transcription by a "blocking"-type mechanism and that CRY-PER inhibits CLOCK-BMAL1 by a "displacement"-type mechanism. While the mechanism of CRY-mediated repression was explained by both in vitro and in vivo experiments, the CRY-PER-mediated repression in vivo seemed in conflict with the in vitro data demonstrating PER removes CRY from the CLOCK-BMAL1-E-box complex. Here, we show that CRY-PER participates in the displacement-type repression by recruiting CK1δ to the nucleus and mediating an increased local concentration of CK1δ at CLOCK-BMAL1-bound promoters/enhancers and thus promoting the phosphorylation of CLOCK and dissociation of CLOCK-BMAL1 along with CRY from the E-box. Our findings bring clarity to the role of PER in the dynamic nature of the repressive phase of the TTFL.
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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.