ArticleMolecular systems biology2012
A mechanism for robust circadian timekeeping via stoichiometric balance.
Article in Molecular systems biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed.
- GenAI-Net: A generative AI framework for automated biomolecular network design.Science advances · 2026Article
- Selection on PER2 Phosphorylation Regulation Underlies Atypical Mammalian Circadian Rhythms.Ecology and evolution · 2026Article
- A compartmentalized SCN model explains temperature resistance through interregional phase differences.PLoS computational biology · 2026Article
- Stoichiometric balance and sustained rhythms.Journal of mathematical biology · 2026Article
- Biochemical mechanism of the mammalian circadian clock.FEBS letters · 2026Review
- Topological Environment in Genetic and Metabolic Networks.bioRxiv : the preprint server for biology · 2026Article
- An Automated Organotypic SCN Culture System Revealing Novel Insights into VIP Regulation of Circadian Rhythm.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immediate nuclear accumulation of BMAL1 to regulate cellular circadian clock synchronization.Communications biology · 2025Article
- Low temperature abolishes human cellular circadian rhythm through Hopf bifurcation.NPJ systems biology and applications · 2025Article
- How cells tame noise while maintaining ultrasensitive transcriptional responses.PLoS computational biology · 2025Article
- Sinusoidal regulation reduces circadian period variability.Scientific reports · 2025Article
- Circadian clock model with sequestration repression motif: existence of periodic orbits and entrainment properties.Interface focus · 2025Article
- Modeling the geometry of circadian synchronization and period across aging.Biogerontology · 2025Article
- Combining lineage correlations and a small molecule inhibitor to detect circadian control of the cell cycle.iScience · 2025Article
- Abundant clock proteins point to missing molecular regulation in the plant circadian clock.Molecular systems biology · 2025Article
- From homogeneity to heterogeneity: Refining stochastic simulations of gene regulation.Computational and structural biotechnology journal · 2025Article
- Phosphorylation of DNA-binding domains of CLOCK-BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Temperature compensation through kinetic regulation in biochemical oscillators.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A robust ultrasensitive transcriptional switch in noisy cellular environments.NPJ systems biology and applications · 2024Article
- Circadian regulation of sinoatrial nodal cell pacemaking function: Dissecting the roles of autonomic control, body temperature, and local circadian rhythmicity.PLoS computational biology · 2024Article
75 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Circadian (∼24 h) timekeeping is essential for the lives of many organisms. To understand the biochemical mechanisms of this timekeeping, we have developed a detailed mathematical model of the mammalian circadian clock. Our model can accurately predict diverse experimental data including the phenotypes of mutations or knockdown of clock genes as well as the time courses and relative expression of clock transcripts and proteins. Using this model, we show how a universal motif of circadian timekeeping, where repressors tightly bind activators rather than directly binding to DNA, can generate oscillations when activators and repressors are in stoichiometric balance. Furthermore, we find that an additional slow negative feedback loop preserves this stoichiometric balance and maintains timekeeping with a fixed period. The role of this mechanism in generating robust rhythms is validated by analysis of a simple and general model and a previous model of the Drosophila circadian clock. We propose a double-negative feedback loop design for biological clocks whose period needs to be tightly regulated even with large changes in gene dosage.
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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.