ArticleCell systems2023
Transcriptional kinetic synergy: A complex landscape revealed by integrating modeling and synthetic biology.
Article in Cell systems, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Stable epigenetic states set single-cell activation thresholds in mammalian expression systems.bioRxiv : the preprint server for biology · 2026Article
- Decoupling between activation time and steady-state level in input-output responses.PLoS computational biology · 2026Article
- Model-guided design of regulatable promoters for synthetic biology.Current opinion in microbiology · 2026Review
- UBIQUITOUS FUNCTIONAL SYNERGY PARTIALLY EXPLAINS WHY MOST TRANSCRIPTION FACTOR BINDING IS NON-FUNCTIONAL.bioRxiv : the preprint server for biology · 2026Article
- Emergence of activation or repression in transcriptional control under a fixed molecular context.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Decoupling between activation time and steady-state level in input-output responses.bioRxiv : the preprint server for biology · 2025Article
- The chronODE framework for modelling multi-omic time series with ordinary differential equations and machine learning.Nature communications · 2025Article
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- A systematic survey of TF function in E. coli suggests RNAP stabilization is a prevalent strategy for both repressors and activators.Nucleic acids research · 2025Article
- Activation-derepression synergy enables a bHLH network to coordinate a signal-specific fate response.Cell reports · 2024Article
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- Article
- Transcriptional synergy in human aortic endothelial cells is vulnerable to combination p300/CBP and BET bromodomain inhibition.iScience · 2024Article
- Comparative cofactor screens show the influence of transactivation domains and core promoters on the mechanisms of transcription.Nature genetics · 2024Article
- Regulatory properties of transcription factors with diverse mechanistic function.PLoS computational biology · 2024Article
- The Hill function is the universal Hopfield barrier for sharpness of input-output responses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Hill function is the universal Hopfield barrier for sharpness of input-output responses.bioRxiv : the preprint server for biology · 2024Article
- Single-molecule chromatin configurations link transcription factor binding to expression in human cells.bioRxiv : the preprint server for biology · 2024Article
- Transcription factor interactions explain the context-dependent activity of CRX binding sites.PLoS computational biology · 2024Article
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8 authors at 2 institutions in 1 country.
Funding
Abstract
Transcription factors (TFs) control gene expression, often acting synergistically. Classical thermodynamic models offer a biophysical explanation for synergy based on binding cooperativity and regulated recruitment of RNA polymerase. Because transcription requires polymerase to transition through multiple states, recent work suggests that "kinetic synergy" can arise through TFs acting on distinct steps of the transcription cycle. These types of synergy are not mutually exclusive and are difficult to disentangle conceptually and experimentally. Here, we model and build a synthetic circuit in which TFs bind to a single shared site on DNA, such that TFs cannot synergize by simultaneous binding. We model mRNA production as a function of both TF binding and regulation of the transcription cycle, revealing a complex landscape dependent on TF concentration, DNA binding affinity, and regulatory activity. We use synthetic TFs to confirm that the transcription cycle must be integrated with recruitment for a quantitative understanding of gene regulation.
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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.