ArticleNucleic acids research2014
Deep sequencing of large library selections allows computational discovery of diverse sets of zinc fingers that bind common targets.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.American journal of human genetics · 2025Article
- Mint/X11 PDZ domains from non-bilaterian animals recognize and bind CaScientific reports · 2024Article
- Keep Fingers on the CpG Islands.Epigenomes · 2024Article
- Structure-based learning to predict and model protein-DNA interactions and transcription-factor co-operativity inNAR genomics and bioinformatics · 2024Article
- Structures of CTCF-DNA complexes including all 11 zinc fingers.Nucleic acids research · 2023Article
- A universal deep-learning model for zinc finger design enables transcription factor reprogramming.Nature biotechnology · 2023Article
- Single base-pair resolution analysis of DNA binding motif with MoMotif reveals an oncogenic function of CTCF zinc-finger 1 mutation.Nucleic acids research · 2022Article
- Article
- CRISPR/Cas-Dependent and Nuclease-FreeHuman gene therapy · 2021Review
- Engineered dual selection for directed evolution of SpCas9 PAM specificity.Nature communications · 2021Article
- On the prediction of DNA-binding preferences of C2H2-ZF domains using structural models: application on human CTCF.NAR genomics and bioinformatics · 2020Article
- The geometric influence on the Cys2His2 zinc finger domain and functional plasticity.Nucleic acids research · 2020Article
- A Multireporter Bacterial 2-Hybrid Assay for the High-Throughput and Dynamic Assay of PDZ Domain-Peptide Interactions.ACS synthetic biology · 2019Article
- Integrating gene synthesis and microfluidic protein analysis for rapid protein engineering.Nucleic acids research · 2016Article
- Pervasive variation of transcription factor orthologs contributes to regulatory network evolution.PLoS genetics · 2015Article
- A systematic survey of the Cys2His2 zinc finger DNA-binding landscape.Nucleic acids research · 2015Article
- Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers.The Biochemical journal · 2014Review
- Engineering synthetic TALE and CRISPR/Cas9 transcription factors for regulating gene expression.Methods (San Diego, Calif.) · 2014Article
- Diversification of transcription factor paralogs via noncanonical modularity in C2H2 zinc finger DNA binding.Molecular cell · 2014Article
- The functional significance of common polymorphisms in zinc finger transcription factors.G3 (Bethesda, Md.) · 2014Article
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Authors and funding
5 authors.
Funding
Abstract
The Cys2His2 zinc finger (ZF) is the most frequently found sequence-specific DNA-binding domain in eukaryotic proteins. The ZF's modular protein-DNA interface has also served as a platform for genome engineering applications. Despite decades of intense study, a predictive understanding of the DNA-binding specificities of either natural or engineered ZF domains remains elusive. To help fill this gap, we developed an integrated experimental-computational approach to enrich and recover distinct groups of ZFs that bind common targets. To showcase the power of our approach, we built several large ZF libraries and demonstrated their excellent diversity. As proof of principle, we used one of these ZF libraries to select and recover thousands of ZFs that bind several 3-nt targets of interest. We were then able to computationally cluster these recovered ZFs to reveal several distinct classes of proteins, all recovered from a single selection, to bind the same target. Finally, for each target studied, we confirmed that one or more representative ZFs yield the desired specificity. In sum, the described approach enables comprehensive large-scale selection and characterization of ZF specificities and should be a great aid in furthering our understanding of the ZF domain.
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