ArticleeLife2020
Gene regulation gravitates toward either addition or multiplication when combining the effects of two signals.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
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- Microenvironmental signals combine to induce non-additive molecular and phenotypic responses in mammary epithelial cells.iScience · 2025Article
- Integrating recombinase-based feedback and feedforward control for optimal resource decoupling.Nucleic acids research · 2025Article
- Transition paths across the epithelial-mesenchymal transition landscape are dictated by network logic.Development (Cambridge, England) · 2025Article
- Modeling the dynamics of EMT reveals genes associated with pan-cancer intermediate states and plasticity.NPJ systems biology and applications · 2025Article
- Interpreting cis-regulatory interactions from large-scale deep neural networks.Nature genetics · 2024Article
- Stochastic Modeling of Biophysical Responses to Perturbation.bioRxiv : the preprint server for biology · 2024Article
- InterpretingbioRxiv : the preprint server for biology · 2024Article
- Disrupting cellular memory to overcome drug resistance.Nature communications · 2023Article
- SeATAC: a tool for exploring the chromatin landscape and the role of pioneer factors.Genome biology · 2023Article
- There's Plenty of Room Right Here: Biological Systems as Evolved, Overloaded, Multi-Scale Machines.Biomimetics (Basel, Switzerland) · 2023Article
- Changes in chromatin accessibility are not concordant with transcriptional changes for single-factor perturbations.Molecular systems biology · 2022Article
- Artificial neural networks enable genome-scale simulations of intracellular signaling.Nature communications · 2022Article
- Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change.Frontiers in endocrinology · 2022Article
- The dynamic, combinatorial cis-regulatory lexicon of epidermal differentiation.Nature genetics · 2021Article
- Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Two different cell signals often affect transcription of the same gene. In such cases, it is natural to ask how the combined transcriptional response compares to the individual responses. The most commonly used mechanistic models predict additive or multiplicative combined responses, but a systematic genome-wide evaluation of these predictions is not available. Here, we analyzed the transcriptional response of human MCF-7 cells to retinoic acid and TGF-β, applied individually and in combination. The combined transcriptional responses of induced genes exhibited a range of behaviors, but clearly favored both additive and multiplicative outcomes. We performed paired chromatin accessibility measurements and found that increases in accessibility were largely additive. There was some association between super-additivity of accessibility and multiplicative or super-multiplicative combined transcriptional responses, while sub-additivity of accessibility associated with additive transcriptional responses. Our findings suggest that mechanistic models of combined transcriptional regulation must be able to reproduce a range of behaviors.
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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.