ArticleGenome research2017
Large-scale mapping of gene regulatory logic reveals context-dependent repression by transcriptional activators.
Article in Genome research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Unlocking the Regulatory Genome: Interpreting the Clinical Impact of Noncoding Variants in Genetic Cardiomyopathies.Circulation. Genomic and precision medicine · 2026Review
- Dual-channel optogenetics in yeast for multiplexed light-based control of cellular processes and pathways.Nature communications · 2026Article
- Abundant repressor binding sites in human enhancers are associated with the fine-tuning of gene regulation.iScience · 2025Article
- Article
- Optimized reporters for multiplexed detection of transcription factor activity.bioRxiv : the preprint server for biology · 2024Article
- Generating information-dense promoter sequences with optimal string packing.PLoS computational biology · 2024Article
- Regulatory properties of transcription factors with diverse mechanistic function.PLoS computational biology · 2024Article
- T-FINDER: A highly sensitive, pan-HLA platform for functional T cell receptor and ligand discovery.Science advances · 2024Article
- Transcription factor interactions explain the context-dependent activity of CRX binding sites.PLoS computational biology · 2024Article
- Optimisation of TP53 reporters by systematic dissection of synthetic TP53 response elements.Nucleic acids research · 2023Article
- Precision engineering of biological function with large-scale measurements and machine learning.PloS one · 2023Article
- Heterogenous circulating miRNA changes in ME/CFS converge on a unified cluster of target genes: A computational analysis.PloS one · 2023Article
- Article
- Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation.Nature communications · 2022Article
- A balancing act in transcription regulation by response regulators: titration of transcription factor activity by decoy DNA binding sites.Nucleic acids research · 2021Article
- Multiplexed characterization of rationally designed promoter architectures deconstructs combinatorial logic for IPTG-inducible systems.Nature communications · 2021Article
- Capturing and Understanding the Dynamics and Heterogeneity of Gene Expression in the Living Cell.International journal of molecular sciences · 2020Review
- Design of Large-Scale Reporter Construct Arrays for Dynamic, Live Cell Systems Biology.ACS synthetic biology · 2018Article
- In silico design of context-responsive mammalian promoters with user-defined functionality.Nucleic acids research · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription factors (TFs) are key mediators that propagate extracellular and intracellular signals through to changes in gene expression profiles. However, the rules by which promoters decode the amount of active TF into target gene expression are not well understood. To determine the mapping between promoter DNA sequence, TF concentration, and gene expression output, we have conducted in budding yeast a large-scale measurement of the activity of thousands of designed promoters at six different levels of TF. We observe that maximum promoter activity is determined by TF concentration and not by the number of binding sites. Surprisingly, the addition of an activator site often reduces expression. A thermodynamic model that incorporates competition between neighboring binding sites for a local pool of TF molecules explains this behavior and accurately predicts both absolute expression and the amount by which addition of a site increases or reduces expression. Taken together, our findings support a model in which neighboring binding sites interact competitively when TF is limiting but otherwise act additively.
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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.