ArticleProceedings of the National Academy of Sciences of the United States of America2018
Specificity landscapes unmask submaximal binding site preferences of transcription factors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- DeepPNI: a language- and graph-based model for mutation-driven protein-nucleic acid binding energetics.Nucleic acids research · 2026Article
- Synthetic ZFTA fusions pinpoint disordered protein domain acquisition as a mechanism of brain tumorigenesis.Nature cell biology · 2025Article
- Mechanisms for DNA Interplay in Eukaryotic Transcription Factors.Annual review of biophysics · 2025Review
- Using synthetic genome readers/regulators to interrogate chromatin processes: A brief review.Methods (San Diego, Calif.) · 2024Review
- DNA binding analysis of rare variants in homeodomains reveals homeodomain specificity-determining residues.Nature communications · 2024Article
- KaScape: a sequencing-based method for global characterization of protein‒DNA binding affinity.Scientific reports · 2023Article
- Hidden modes of DNA binding by human nuclear receptors.Nature communications · 2023Article
- Flexibility of flanking DNA is a key determinant of transcription factor affinity for the core motif.Biophysical journal · 2022Article
- FOXL2 and FOXA1 cooperatively assemble on the TP53 promoter in alternative dimer configurations.Nucleic acids research · 2022Article
- Fusion proteins form onco-condensates.Nature structural & molecular biology · 2021Article
- Mechanism of conditional partner selectivity in MITF/TFE family transcription factors with a conserved coiled coil stammer motif.Nucleic acids research · 2020Article
- Single position substitution of hairpin pyrrole-imidazole polyamides imparts distinct DNA-binding profiles across the human genome.PloS one · 2020Article
- De novo design of programmable inducible promoters.Nucleic acids research · 2019Article
- Low-Affinity Binding Sites and the Transcription Factor Specificity Paradox in Eukaryotes.Annual review of cell and developmental biology · 2019Review
- Flexibility and structure of flanking DNA impact transcription factor affinity for its core motif.Nucleic acids research · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
We have developed Differential Specificity and Energy Landscape (DiSEL) analysis to comprehensively compare DNA-protein interactomes (DPIs) obtained by high-throughput experimental platforms and cutting edge computational methods. While high-affinity DNA binding sites are identified by most methods, DiSEL uncovered nuanced sequence preferences displayed by homologous transcription factors. Pairwise analysis of 726 DPIs uncovered homolog-specific differences at moderate- to low-affinity binding sites (submaximal sites). DiSEL analysis of variants of 41 transcription factors revealed that many disease-causing mutations result in allele-specific changes in binding site preferences. We focused on a set of highly homologous factors that have different biological roles but "read" DNA using identical amino acid side chains. Rather than direct readout, our results indicate that DNA noncontacting side chains allosterically contribute to sculpt distinct sequence preferences among closely related members of transcription factor families.
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