ArticleNucleic acids research2023
High-throughput data and modeling reveal insights into the mechanisms of cooperative DNA-binding by transcription factor proteins.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 19 citations in OpenAlex.
- Systematic functional dissection of germline noncoding risk variants impacting clonal hematopoiesis.bioRxiv : the preprint server for biology · 2026Article
- Genome-wide nucleosome and transcription factor responses to genetic perturbations reveal chromatin-mediated mechanisms of transcriptional regulation.Genome research · 2026Article
- Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs.bioRxiv : the preprint server for biology · 2025Article
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- Interpreting regulatory mechanisms of Hippo signaling through a deep learning sequence model.Cell genomics · 2025Article
- Human Stress Response Specificity through Bioresonance Selectivity.bioRxiv : the preprint server for biology · 2025Article
- Article
- From homogeneity to heterogeneity: Refining stochastic simulations of gene regulation.Computational and structural biotechnology journal · 2025Article
- BindCompare: a novel integrated protein-nucleic acid binding analysis platform.Bioinformatics (Oxford, England) · 2024Article
- TIANA: transcription factors cooperativity inference analysis with neural attention.BMC bioinformatics · 2024Article
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5 authors at 1 institution in 1 country.
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Abstract
Cooperative DNA-binding by transcription factor (TF) proteins is critical for eukaryotic gene regulation. In the human genome, many regulatory regions contain TF-binding sites in close proximity to each other, which can facilitate cooperative interactions. However, binding site proximity does not necessarily imply cooperative binding, as TFs can also bind independently to each of their neighboring target sites. Currently, the rules that drive cooperative TF binding are not well understood. In addition, it is oftentimes difficult to infer direct TF-TF cooperativity from existing DNA-binding data. Here, we show that in vitro binding assays using DNA libraries of a few thousand genomic sequences with putative cooperative TF-binding events can be used to develop accurate models of cooperativity and to gain insights into cooperative binding mechanisms. Using factors ETS1 and RUNX1 as our case study, we show that the distance and orientation between ETS1 sites are critical determinants of cooperative ETS1-ETS1 binding, while cooperative ETS1-RUNX1 interactions show more flexibility in distance and orientation and can be accurately predicted based on the affinity and sequence/shape features of the binding sites. The approach described here, combining custom experimental design with machine-learning modeling, can be easily applied to study the cooperative DNA-binding patterns of any TFs.
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