ArticleMolecular systems biology2010
Short-term memory in gene induction reveals the regulatory principle behind stochastic IL-4 expression.
Article in Molecular systems biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 86 citations in OpenAlex.
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- Dissecting the dynamic transcriptional landscape of early T helper cell differentiation into Th1, Th2, and Th1/2 hybrid cells.Frontiers in immunology · 2022Article
- In search of lost time: Enhancers as modulators of timing in lymphocyte development and differentiation.Immunological reviews · 2021Review
- Partitioning stable and unstable expression level variation in cell populations: A theoretical framework and its application to the T cell receptor.PLoS computational biology · 2020Article
- Gene Regulatory Strategies that Decode the Duration of NFκB Dynamics Contribute to LPS- versus TNF-Specific Gene Expression.Cell systems · 2020Article
- Quantifying the Stability of Coupled Genetic and Epigenetic Switches With Variational Methods.Frontiers in genetics · 2020Article
- Importance of Type I and III Interferons at Respiratory and Intestinal Barrier Surfaces.Frontiers in immunology · 2020Review
- Order by chance: origins and benefits of stochasticity in immune cell fate control.Current opinion in systems biology · 2019Article
- Multi-modality in gene regulatory networks with slow promoter kinetics.PLoS computational biology · 2019Article
- Analysis of Single-Cell Gene Pair Coexpression Landscapes by Stochastic Kinetic Modeling Reveals Gene-Pair Interactions in Development.Frontiers in genetics · 2019Article
- Stochastic multistationarity in a model of the hematopoietic stem cell differentiation network.Proceedings of the ... IEEE Conference on Decision & Control. IEEE Conference on Decision & Control · 2018Article
- Nongenetic origins of cell-to-cell variability in B lymphocyte proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Mathematical modeling identifies Lck as a potential mediator for PD-1 induced inhibition of early TCR signaling.PloS one · 2018Article
- Simulation of Stimulation: Cytokine Dosage and Cell Cycle Crosstalk Driving Timing-Dependent T Cell Differentiation.Frontiers in physiology · 2018Article
- Environment Tunes Propagation of Cell-to-Cell Variation in the Human Macrophage Gene Network.Cell systems · 2017Article
- IL-4 Haploinsufficiency Specifically Impairs IgE Responses against Allergens in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Solving Immunology?Trends in immunology · 2017Review
- DNA-Binding Kinetics Determines the Mechanism of Noise-Induced Switching in Gene Networks.Biophysical journal · 2015Article
- Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins.Cell reports · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although cell-to-cell variability has been recognized as an unavoidable consequence of stochasticity in gene expression, it may also serve a functional role for tuning physiological responses within a cell population. In the immune system, remarkably large variability in the expression of cytokine genes has been observed in homogeneous populations of lymphocytes, but the underlying molecular mechanisms are incompletely understood. Here, we study the interleukin-4 gene (il4) in T-helper lymphocytes, combining mathematical modeling with the experimental quantification of expression variability and critical parameters. We show that a stochastic rate-limiting step upstream of transcription initiation, but acting at the level of an individual allele, controls il4 expression. Only a fraction of cells reaches an active, transcription-competent state in the transient time window determined by antigen stimulation. We support this finding by experimental evidence of a previously unknown short-term memory that was predicted by the model to arise from the long lifetime of the active state. Our analysis shows how a stochastic mechanism acting at the chromatin level can be integrated with transcriptional regulation to quantitatively control cell-to-cell variability.
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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.