ArticlePLoS computational biology2008
Multistable decision switches for flexible control of epigenetic differentiation.
Article in PLoS computational biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed.
- Oscillatory co-expression of HES1 and HES5 enables a hybrid state in a cross-repressive transcription factor regulatory motif.Development (Cambridge, England) · 2026Article
- Network hypermotifs in biological systems: structure, dynamics, and functional implications.NPJ systems biology and applications · 2026Review
- GRiNS: a python library for simulating gene regulatory network dynamics.BMC bioinformatics · 2025Article
- Emergent dynamics of cellular decision making in multi-node mutually repressive regulatory networks.Journal of the Royal Society, Interface · 2025Article
- Polygenic prediction and gene regulation networks.Royal Society open science · 2025Article
- Operating principles of interconnected feedback loops driving cell fate transitions.NPJ systems biology and applications · 2025Article
- OneSC: a computational platform for recapitulating cell state transitions.Bioinformatics (Oxford, England) · 2024Article
- Multistability and predominant hybrid phenotypes in a four node mutually repressive network of Th1/Th2/Th17/Treg differentiation.NPJ systems biology and applications · 2024Article
- Enhanced cellular longevity arising from environmental fluctuations.Cell systems · 2024Article
- OneSC: A computational platform for recapitulating cell state transitions.bioRxiv : the preprint server for biology · 2024Article
- Origin, heterogeneity, and interconversion of noncanonical bistable switches from the positive feedback loops under dual signaling.iScience · 2023Article
- What Makes a Functional Gene Regulatory Network? A Circuit Motif Analysis.The journal of physical chemistry. B · 2022Article
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- Switching off: The phenotypic transition to the uninduced state of the lactose uptake pathway.Biophysical journal · 2022Article
- Monostability and bistability of biological switches.Journal of mathematical biology · 2021Article
- Review
- Feedback, Crosstalk and Competition: Ingredients for Emergent Non-Linear Behaviour in the PI3K/mTOR Signalling Network.International journal of molecular sciences · 2021Review
- Memorizing environmental signals through feedback and feedforward loops.Current opinion in cell biology · 2021Review
- Topological signatures in regulatory network enable phenotypic heterogeneity in small cell lung cancer.eLife · 2021Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is now recognized that molecular circuits with positive feedback can induce two different gene expression states (bistability) under the very same cellular conditions. Whether, and how, cells make use of the coexistence of a larger number of stable states (multistability) is however largely unknown. Here, we first examine how autoregulation, a common attribute of genetic master regulators, facilitates multistability in two-component circuits. A systematic exploration of these modules' parameter space reveals two classes of molecular switches, involving transitions in bistable (progression switches) or multistable (decision switches) regimes. We demonstrate the potential of decision switches for multifaceted stimulus processing, including strength, duration, and flexible discrimination. These tasks enhance response specificity, help to store short-term memories of recent signaling events, stabilize transient gene expression, and enable stochastic fate commitment. The relevance of these circuits is further supported by biological data, because we find them in numerous developmental scenarios. Indeed, many of the presented information-processing features of decision switches could ultimately demonstrate a more flexible control of epigenetic differentiation.
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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.