ArticleInterface focus2022
Combined multiple transcriptional repression mechanisms generate ultrasensitivity and oscillations.
Article in Interface focus, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- GenAI-Net: A generative AI framework for automated biomolecular network design.Science advances · 2026Article
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- How cells tame noise while maintaining ultrasensitive transcriptional responses.PLoS computational biology · 2025Article
- Tuning Ultrasensitivity in Genetic Logic Gates Using Antisense RNA Feedback.ACS synthetic biology · 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
- Entrainment and multi-stability of the p53 oscillator in human cells.Cell systems · 2024Article
- 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
- Simplifications and approximations in a single-gene circuit modeling.Scientific reports · 2024Article
- A robust ultrasensitive transcriptional switch in noisy cellular environments.NPJ systems biology and applications · 2024Article
- Article
- An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells.NPJ systems biology and applications · 2023Article
- The ups and downs of biological oscillators: a comparison of time-delayed negative feedback mechanisms.Journal of the Royal Society, Interface · 2023Article
- Cell cycle oscillations driven by two interlinked bistable switches.Molecular biology of the cell · 2023Article
- Negative feedback systems for modelling NF-κB transcription factor oscillatory activity.TranscriptionArticle
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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
Transcriptional repression can occur via various mechanisms, such as blocking, sequestration and displacement. For instance, the repressors can hold the activators to prevent binding with DNA or can bind to the DNA-bound activators to block their transcriptional activity. Although the transcription can be completely suppressed with a single mechanism, multiple repression mechanisms are used together to inhibit transcriptional activators in many systems, such as circadian clocks and NF-κB oscillators. This raises the question of what advantages arise if seemingly redundant repression mechanisms are combined. Here, by deriving equations describing the multiple repression mechanisms, we find that their combination can synergistically generate a sharply ultrasensitive transcription response and thus strong oscillations. This rationalizes why the multiple repression mechanisms are used together in various biological oscillators. The critical role of such combined transcriptional repression for strong oscillations is further supported by our analysis of formerly identified mutations disrupting the transcriptional repression of the mammalian circadian clock. The hitherto unrecognized source of the ultrasensitivity, the combined transcriptional repressions, can lead to robust synthetic oscillators with a previously unachievable simple design.
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