ArticleNature communications2020
Mechanistic insights into transcription factor cooperativity and its impact on protein-phenotype interactions.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed.
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- A role for pH dynamics regulating transcription factor DNA-binding selectivity.Nucleic acids research · 2025Article
- Enhancers in Plant Development, Adaptation and Evolution.Plant & cell physiology · 2025Review
- Quantification and potential functional relevance of binding cooperativity of adjacent transcription factors on DNA.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Integrating genetic variation with deep learning provides context for variants impacting transcription factor binding during embryogenesis.Genome research · 2025Article
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- Light-dependent flavin redox and adduct states control the conformation and DNA-binding activity of the transcription factor EL222.Nucleic acids research · 2025Article
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- CoTF-reg reveals cooperative transcription factors in oligodendrocyte gene regulation using single-cell multi-omics.Communications biology · 2025Article
- Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.Developmental cell · 2025Article
- NetREm: Network Regression Embeddings reveal cell-type transcription factor coordination for gene regulation.Bioinformatics advances · 2025Article
- Rise and SINE: roles of transcription factors and retrotransposons in zygotic genome activation.Nature reviews. Molecular cell biology · 2025Article
- Systematic identification of interchromosomal interaction networks supports the existence of specialized RNA factories.Genome research · 2024Article
- The STAT3/SETDB2 axis dictates NF-κB-mediated inflammation in macrophages during wound repair.JCI insight · 2024Article
- A large-scale cancer-specific protein-DNA interaction network.Life science alliance · 2024Article
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Authors and funding
7 authors.
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Abstract
Recent high-throughput transcription factor (TF) binding assays revealed that TF cooperativity is a widespread phenomenon. However, a global mechanistic and functional understanding of TF cooperativity is still lacking. To address this, here we introduce a statistical learning framework that provides structural insight into TF cooperativity and its functional consequences based on next generation sequencing data. We identify DNA shape as driver for cooperativity, with a particularly strong effect for Forkhead-Ets pairs. Follow-up experiments reveal a local shape preference at the Ets-DNA-Forkhead interface and decreased cooperativity upon loss of the interaction. Additionally, we discover many functional associations for cooperatively bound TFs. Examination of the link between FOXO1:ETV6 and lymphomas reveals that their joint expression levels improve patient clinical outcome stratification. Altogether, our results demonstrate that inter-family cooperative TF binding is driven by position-specific DNA readout mechanisms, which provides an additional regulatory layer for downstream biological functions.
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