ArticleNucleic acids research2015
A structural approach reveals how neighbouring C2H2 zinc fingers influence DNA binding specificity.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Study on the molecular mechanism of colony strength of Apis cerana cerana based on transcriptomics.BMC genomics · 2026Article
- Zinc-finger transcription factor Fzf1 binds to its target DNA in a non-canonical manner.Nucleic acids research · 2026Article
- The evolutionary entanglement of flipons with zinc fingers and retroelements has engendered a large family of Z-DNA and G-quadruplex binding proteins.Open biology · 2025Article
- Charting the regulatory landscape of TP53 on transposable elements in cancer.Genome research · 2025Article
- Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteins.Nature communications · 2024Article
- New Drosophila promoter-associated architectural protein Mzfp1 interacts with CP190 and is required for housekeeping gene expression and insulator activity.Nucleic acids research · 2024Article
- A universal deep-learning model for zinc finger design enables transcription factor reprogramming.Nature biotechnology · 2023Article
- Structure of SALL4 zinc finger domain reveals link between AT-rich DNA binding and Okihiro syndrome.Life science alliance · 2023Article
- Human zygotic genome activation is initiated from paternal genome.Cell discovery · 2023Article
- The Essential Role of Prolines and Their Conformation in Allosteric Regulation of Kaiso Zinc Finger DNA-Binding Activity by the Adjacent C-Terminal Loop.International journal of molecular sciences · 2022Article
- Neural network modeling of differential binding between wild-type and mutant CTCF reveals putative binding preferences for zinc fingers 1-2.BMC genomics · 2022Article
- Structure-function relationships explain CTCF zinc finger mutation phenotypes in cancer.Cellular and molecular life sciences : CMLS · 2021Article
- Points of View on the Tools for Genome/Gene Editing.International journal of molecular sciences · 2021Review
- The geometric influence on the Cys2His2 zinc finger domain and functional plasticity.Nucleic acids research · 2020Article
- Balance between asymmetry and abundance in multi-domain DNA-binding proteins may regulate the kinetics of their binding to DNA.PLoS computational biology · 2020Article
- Glass confers rhabdomeric photoreceptor identity inEvoDevo · 2019Article
- Diversification of transcription factor-DNA interactions and the evolution of gene regulatory networks.Wiley interdisciplinary reviews. Systems biology and medicine · 2018Review
- Obesity-induced protein carbonylation in murine adipose tissue regulates the DNA-binding domain of nuclear zinc finger proteins.The Journal of biological chemistry · 2018Article
- Two critical positions in zinc finger domains are heavily mutated in three human cancer types.PLoS computational biology · 2018Article
- True equilibrium measurement of transcription factor-DNA binding affinities using automated polarization microscopy.Nature communications · 2018Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Development of an accurate protein-DNA recognition code that can predict DNA specificity from protein sequence is a central problem in biology. C2H2 zinc fingers constitute by far the largest family of DNA binding domains and their binding specificity has been studied intensively. However, despite decades of research, accurate prediction of DNA specificity remains elusive. A major obstacle is thought to be the inability of current methods to account for the influence of neighbouring domains. Here we show that this problem can be addressed using a structural approach: we build structural models for all C2H2-ZF-DNA complexes with known binding motifs and find six distinct binding modes. Each mode changes the orientation of specificity residues with respect to the DNA, thereby modulating base preference. Most importantly, the structural analysis shows that residues at the domain interface strongly and predictably influence the binding mode, and hence specificity. Accounting for predicted binding mode significantly improves prediction accuracy of predicted motifs. This new insight into the fundamental behaviour of C2H2-ZFs has implications for both improving the prediction of natural zinc finger-binding sites, and for prioritizing further experiments to complete the code. It also provides a new design feature for zinc finger engineering.
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