ArticleNucleic acids research2011
Sequence specificity is obtained from the majority of modular C2H2 zinc-finger arrays.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 90 citations in OpenAlex.
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- Balance between asymmetry and abundance in multi-domain DNA-binding proteins may regulate the kinetics of their binding to DNA.PLoS computational biology · 2020Article
- Similarity regression predicts evolution of transcription factor sequence specificity.Nature genetics · 2019Article
- The bZIP mutant CEBPB (V285A) has sequence specific DNA binding propensities similar to CREB1.Biochimica et biophysica acta. Gene regulatory mechanisms · 2019Article
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- Article
- Cys₂/His₂ Zinc-Finger Proteins in Transcriptional Regulation of Flower Development.International journal of molecular sciences · 2018Review
- Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA.Biochemical and biophysical research communications · 2018Article
- Structural basis for the ability of MBD domains to bind methyl-CG and TG sites in DNA.The Journal of biological chemistry · 2018Article
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Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
C2H2 zinc fingers (C2H2-ZFs) are the most prevalent type of vertebrate DNA-binding domain, and typically appear in tandem arrays (ZFAs), with sequential C2H2-ZFs each contacting three (or more) sequential bases. C2H2-ZFs can be assembled in a modular fashion, providing one explanation for their remarkable evolutionary success. Given a set of modules with defined three-base specificities, modular assembly also presents a way to construct artificial proteins with specific DNA-binding preferences. However, a recent survey of a large number of three-finger ZFAs engineered by modular assembly reported high failure rates (∼70%), casting doubt on the generality of modular assembly. Here, we used protein-binding microarrays to analyze 28 ZFAs that failed in the aforementioned study. Most (17) preferred specific sequences, which in all but one case resembled the intended target sequence. Like natural ZFAs, the engineered ZFAs typically yielded degenerate motifs, binding dozens to hundreds of related individual sequences. Thus, the failure of these proteins in previous assays is not due to lack of sequence-specific DNA-binding activity. Our findings underscore the relevance of individual C2H2-ZF sequence specificities within tandem arrays, and support the general ability of modular assembly to produce ZFAs with sequence-specific DNA-binding activity.
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Registered trials
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