ArticleCell systems2018
Divergence in DNA Specificity among Paralogous Transcription Factors Contributes to Their Differential In Vivo Binding.
Article in Cell systems, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Evolutionary causes and consequences of gene duplication.Nature reviews. Genetics · 2026Review
- PoolParty: streamlined design of DNA sequence libraries in Python.bioRxiv : the preprint server for biology · 2026Article
- Quantifying transcription factor specificity with advanced DNA universal microarrays featuring long and modified binding sites.Nucleic acids research · 2025Article
- Article
- Mechanisms driving functional divergence of transcription factor paralogs.The New phytologist · 2025Review
- Systematic DNA nicking reveals the structural logic of protein recognition.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms for DNA Interplay in Eukaryotic Transcription Factors.Annual review of biophysics · 2025Review
- Mutations to transcription factor MAX allosterically increase DNA selectivity by altering folding and binding pathways.Nature communications · 2025Article
- RLS-associated MEIS transcription factors control distinct processes in human neural stem cells.Scientific reports · 2024Article
- START domains generate paralog-specific regulons from a single network architecture.Nature communications · 2024Article
- DNA sequence and chromatin differentiate sequence-specific transcription factor binding in the human malaria parasite Plasmodium falciparum.Nucleic acids research · 2024Article
- TFscope: systematic analysis of the sequence features involved in the binding preferences of transcription factors.Genome biology · 2024Article
- Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms.bioRxiv : the preprint server for biology · 2024Article
- High UV damage and low repair, but not cytosine deamination, stimulate mutation hotspots at ETS binding sites in melanoma.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- High-throughput data and modeling reveal insights into the mechanisms of cooperative DNA-binding by transcription factor proteins.Nucleic acids research · 2023Article
- Article
- Double DAP-seq uncovered synergistic DNA binding of interacting bZIP transcription factors.Nature communications · 2023Article
- Context-dependent CpG methylation directs cell-specific binding of transcription factor ZBTB38.Epigenetics · 2022Article
- Flexibility of flanking DNA is a key determinant of transcription factor affinity for the core motif.Biophysical journal · 2022Article
- Elucidating the biology of transcription factor-DNA interaction for accurate identification of cis-regulatory elements.Current opinion in plant biology · 2022Review
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Authors and funding
10 authors.
Funding
Abstract
Paralogous transcription factors (TFs) are oftentimes reported to have identical DNA-binding motifs, despite the fact that they perform distinct regulatory functions. Differential genomic targeting by paralogous TFs is generally assumed to be due to interactions with protein co-factors or the chromatin environment. Using a computational-experimental framework called iMADS (integrative modeling and analysis of differential specificity), we show that, contrary to previous assumptions, paralogous TFs bind differently to genomic target sites even in vitro. We used iMADS to quantify, model, and analyze specificity differences between 11 TFs from 4 protein families. We found that paralogous TFs have diverged mainly at medium- and low-affinity sites, which are poorly captured by current motif models. We identify sequence and shape features differentially preferred by paralogous TFs, and we show that the intrinsic differences in specificity among paralogous TFs contribute to their differential in vivo binding. Thus, our study represents a step forward in deciphering the molecular mechanisms of differential specificity in TF families.
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