ReviewAnnual review of cell and developmental biology2019
Low-Affinity Binding Sites and the Transcription Factor Specificity Paradox in Eukaryotes.
Review in Annual review of cell and developmental biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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Who cites it
138 citing papers in PubMed.
- A transcription factor by any other name - function beyond DNA binding and transactivation.EMBO reports · 2026Review
- GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity and complex DNA binding of many human transcription factors.Nature methods · 2026Article
- Nucleosomes and IDRs suppress promiscuous GCN4 binding on minichromosomes.Nature structural & molecular biology · 2026Article
- Motif-Cluster: Motif driven prioritization of transcription factor binding clusters.PLoS computational biology · 2026Article
- Cis- and trans-regulatory factors contributing to divergent activity of the TDH3 promoter in Saccharomyces yeast.Molecular biology and evolution · 2026Article
- Evolutionary Simulations Reveal Role for Genomic Recombination in the Evolution of Gene Regulatory Network Complexity and Robustness.Genome biology and evolution · 2026Article
- Nonconsensus flanking sequence of hundreds of base pairs around in vivo binding sites: statistical beacons for transcription factor scanning.Nucleic acids research · 2026Article
- Elevated MyoD1 levels expand genome-wide binding and the repertoire of regulated genes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Amplification of MED30 at chromosome 8q24 reprograms MYC binding to low-affinity oncogenic enhancers in cancer cells.Cell reports · 2026Article
- Highly Constrained Kinetic Models for Single-Cell Gene Expression Analysis.bioRxiv : the preprint server for biology · 2026Article
- Probing transcription factor subsets in gene regulatory networks.Algorithms for molecular biology : AMB · 2026Article
- Review
- Bipartite DNA binding domain of transcription factor BCL11B binds clustered short DNA sequence motifs.bioRxiv : the preprint server for biology · 2026Article
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- Article
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- Cell type-specific epigenetic regulatory circuitry of coronary artery disease loci.Nature communications · 2026Article
- Sequence-based modeling of low-affinity transcription factor-DNA binding through deep learning.NAR genomics and bioinformatics · 2026Article
- Quantitative modulation of a spatial enhancer through the biophysical properties of a transcription factor binding site.Science advances · 2026Article
- A structure-guided approach to noncoding variant evaluation for transcription factor binding using AlphaFold 3.Nucleic acids research · 2026Article
78 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Eukaryotic transcription factors (TFs) from the same structural family tend to bind similar DNA sequences, despite the ability of these TFs to execute distinct functions in vivo. The cell partly resolves this specificity paradox through combinatorial strategies and the use of low-affinity binding sites, which are better able to distinguish between similar TFs. However, because these sites have low affinity, it is challenging to understand how TFs recognize them in vivo. Here, we summarize recent findings and technological advancements that allow for the quantification and mechanistic interpretation of TF recognition across a wide range of affinities. We propose a model that integrates insights from the fields of genetics and cell biology to provide further conceptual understanding of TF binding specificity. We argue that in eukaryotes, target specificity is driven by an inhomogeneous 3D nuclear distribution of TFs and by variation in DNA binding affinity such that locally elevated TF concentration allows low-affinity binding sites to be functional.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.