ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2013
Structure-aided prediction of mammalian transcription factor complexes in conserved non-coding elements.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Functional genomics analysis of developing zebrafish and human endoderm reveals highly conservedGenome research · 2026Article
- Article
- The α-globin super-enhancer acts in an orientation-dependent manner.Nature communications · 2025Article
- Motif distribution in genomes gives insights into gene clustering and co-regulation.Nucleic acids research · 2025Article
- Review
- Systematic analysis of low-affinity transcription factor binding site clusters in vitro and in vivo establishes their functional relevance.Nature communications · 2022Article
- WhichTF is functionally important in your open chromatin data?PLoS computational biology · 2022Article
- Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta.International journal of molecular sciences · 2020Article
- Mechanistic insights into transcription factor cooperativity and its impact on protein-phenotype interactions.Nature communications · 2020Article
- A single ChIP-seq dataset is sufficient for comprehensive analysis of motifs co-occurrence with MCOT package.Nucleic acids research · 2019Article
- Combined analysis of dissimilar promoter accessibility and gene expression profiles identifies tissue-specific genes and actively repressed networks.Epigenetics & chromatin · 2019Article
- Independent erosion of conserved transcription factor binding sites points to shared hindlimb, vision and external testes loss in different mammals.Nucleic acids research · 2018Article
- A screen for deeply conserved non-coding GWAS SNPs uncovers a MIR-9-2 functional mutation associated to retinal vasculature defects in human.Nucleic acids research · 2018Article
- Intrinsic DNA binding properties demonstrated for lineage-specifying basic helix-loop-helix transcription factors.Genome research · 2018Article
- Review
- "Reverse Genomics" Predicts Function of Human Conserved Noncoding Elements.Molecular biology and evolution · 2016Article
- Erosion of Conserved Binding Sites in Personal Genomes Points to Medical Histories.PLoS computational biology · 2016Article
- Combinatorial Cis-regulation in Saccharomyces Species.G3 (Bethesda, Md.) · 2016Article
- Changes in the enhancer landscape during early placental development uncover a trophoblast invasion gene-enhancer network.Placenta · 2016Article
- DNA-dependent formation of transcription factor pairs alters their binding specificity.Nature · 2015Article
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4 authors.
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Abstract
Mapping the DNA-binding preferences of transcription factor (TF) complexes is critical for deciphering the functions of cis-regulatory elements. Here, we developed a computational method that compares co-occurring motif spacings in conserved versus unconserved regions of the human genome to detect evolutionarily constrained binding sites of rigid TF complexes. Structural data were used to estimate TF complex physical plausibility, explore overlapping motif arrangements seldom tackled by non-structure-aware methods, and generate and analyse three-dimensional models of the predicted complexes bound to DNA. Using this approach, we predicted 422 physically realistic TF complex motifs at 18% false discovery rate, the majority of which (326, 77%) contain some sequence overlap between binding sites. The set of mostly novel complexes is enriched in known composite motifs, predictive of binding site configurations in TF-TF-DNA crystal structures, and supported by ChIP-seq datasets. Structural modelling revealed three cooperativity mechanisms: direct protein-protein interactions, potentially indirect interactions and 'through-DNA' interactions. Indeed, 38% of the predicted complexes were found to contain four or more bases in which TF pairs appear to synergize through overlapping binding to the same DNA base pairs in opposite grooves or strands. Our TF complex and associated binding site predictions are available as a web resource at http://bejerano.stanford.edu/complex.
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