ArticleBiophysical journal2022
Flexibility of flanking DNA is a key determinant of transcription factor affinity for the core motif.
Article in Biophysical journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 25 citations in OpenAlex.
- Readout of intrinsic and induced DNA shape by homeodomain transcription factor complexes.Biophysical journal · 2026Article
- Novel perspectives on PPARγ regulation: from SPPARMs to the emerging role of lncRNAs in metabolic disorders.International journal of obesity (2005) · 2026Review
- The role of the 2'-OH group in phase separation and percolation transitions of RNA.Nature communications · 2026Article
- Nonconsensus flanking sequence of hundreds of base pairs around in vivo binding sites: statistical beacons for transcription factor scanning.Nucleic acids research · 2026Article
- The Critical Role of the 2'-OH group in Phase Separation and Percolation Transitions of RNA.bioRxiv : the preprint server for biology · 2026Article
- Uncovering the Mechanistic Landscape of Regulatory DNA with Deep Learning.bioRxiv : the preprint server for biology · 2025Article
- Sequence-Dependent Shape and Stiffness of DNA and RNA Double Helices: Hexanucleotide Scale and Beyond.Journal of chemical information and modeling · 2025Article
- ZmSSRP1, transactivated by OPAQUE11, positively regulates starch biosynthesis in maize endosperm.Plant biotechnology journal · 2025Article
- Variations in flanking or less conserved positions of Reb1 and Abf1 consensus binding sites lead to major changes in their ability to modulate nucleosome sliding activity.Biological research · 2025Article
- A high-throughput single-molecule platform to study DNA supercoiling effect on protein-DNA interactions.Nucleic acids research · 2025Article
- Modeling and designing enhancers by introducing and harnessing transcription factor binding units.Nature communications · 2025Article
- Recent advances in designing synthetic plant regulatory modules.Frontiers in plant science · 2025Review
- Predicting DNA structure using a deep learning method.Nature communications · 2024Article
- Probing the role of the protonation state of a minor groove-linker histidine in Exd-Hox-DNA binding.Biophysical journal · 2024Article
- Predictions of DNA mechanical properties at a genomic scale reveal potentially new functional roles of DNA flexibility.NAR genomics and bioinformatics · 2023Article
- Noncanonical binding of transcription factors: time to revisitMolecular biology of the cell · 2023Review
- Computational Modeling of DNA 3D Structures: From Dynamics and Mechanics to Folding.Molecules (Basel, Switzerland) · 2023Review
- Structural predictions of protein-DNA binding: MELD-DNA.Nucleic acids research · 2023Article
- DNA structural properties of DNA binding sites for 21 transcription factors in the mycobacterial genome.Frontiers in cellular and infection microbiology · 2023Article
- It is in the flanks: Conformational flexibility of transcription factor binding sites.Biophysical journal · 2022Article
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2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Selective gene regulation is mediated by recognition of specific DNA sequences by transcription factors (TFs). The extremely challenging task of searching out specific cognate DNA binding sites among several million putative sites within the eukaryotic genome is achieved by complex molecular recognition mechanisms. Elements of this recognition code include the core binding sequence, the flanking sequence context, and the shape and conformational flexibility of the composite binding site. To unravel the extent to which DNA flexibility modulates TF binding, in this study, we employed experimentally guided molecular dynamics simulations of ternary complex of closely related Hox heterodimers Exd-Ubx and Exd-Scr with DNA. Results demonstrate that flexibility signatures embedded in the flanking sequences impact TF binding at the cognate binding site. A DNA sequence has intrinsic shape and flexibility features. While shape features are localized, our analyses reveal that flexibility features of the flanking sequences percolate several basepairs and allosterically modulate TF binding at the core. We also show that lack of flexibility in the motif context can render the cognate site resistant to protein-induced shape changes and subsequently lower TF binding affinity. Overall, this study suggests that flexibility-guided DNA shape, and not merely the static shape, is a key unexplored component of the complex DNA-TF recognition code.
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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 OpenQuestion graph.