ArticleNucleic acids research2023
Prediction of cooperative homeodomain DNA binding sites from high-throughput-SELEX data.
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 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family.Nature communications · 2026Article
- An inducible system to study the regulatory functions of GSX2 in human lateral ganglionic eminence-like progenitors.Developmental biology · 2026Article
- Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family.bioRxiv : the preprint server for biology · 2025Article
- Article
- The ALX4 dimer structure provides insight into how disease alleles impact function.Nature communications · 2025Article
- Identifying the DNA methylation preference of transcription factors using ProtBERT and SVM.PLoS computational biology · 2025Article
- Experimental approaches to investigate biophysical interactions between homeodomain transcription factors and DNA.Biochimica et biophysica acta. Gene regulatory mechanisms · 2025Review
- Modelling a pathological GSX2 variant that selectively alters DNA binding reveals hypomorphic mouse brain defects.Disease models & mechanisms · 2025Article
- Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.Developmental cell · 2025Article
- Homeodomain Involvement in Nuclear HOX Protein Homo- and Heterodimerization.International journal of molecular sciences · 2025Article
- Identifying the "stripe" transcription factors and cooperative binding related to DNA methylation.Communications biology · 2024Article
- Cooperative Gsx2-DNA binding requires DNA bending and a novel Gsx2 homeodomain interface.Nucleic acids research · 2024Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Homeodomain proteins constitute one of the largest families of metazoan transcription factors. Genetic studies have demonstrated that homeodomain proteins regulate many developmental processes. Yet, biochemical data reveal that most bind highly similar DNA sequences. Defining how homeodomain proteins achieve DNA binding specificity has therefore been a long-standing goal. Here, we developed a novel computational approach to predict cooperative dimeric binding of homeodomain proteins using High-Throughput (HT) SELEX data. Importantly, we found that 15 of 88 homeodomain factors form cooperative homodimer complexes on DNA sites with precise spacing requirements. Approximately one third of the paired-like homeodomain proteins cooperatively bind palindromic sequences spaced 3 bp apart, whereas other homeodomain proteins cooperatively bind sites with distinct orientation and spacing requirements. Combining structural models of a paired-like factor with our cooperativity predictions identified key amino acid differences that help differentiate between cooperative and non-cooperative factors. Finally, we confirmed predicted cooperative dimer sites in vivo using available genomic data for a subset of factors. These findings demonstrate how HT-SELEX data can be computationally mined to predict cooperativity. In addition, the binding site spacing requirements of select homeodomain proteins provide a mechanism by which seemingly similar AT-rich DNA sequences can preferentially recruit specific homeodomain factors.
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