Evidence map›Paper›PMID 25593323›Full record

ArticleNucleic acids research2015

A systematic survey of the Cys2His2 zinc finger DNA-binding landscape.

Anton V Persikov, Joshua L Wetzel, Elizabeth F Rowland, Benjamin L Oakes, Denise J Xu, Mona Singh, Marcus B Noyes

Abstract read
In one paragraph

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 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed.

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  3. Expanding the phenotypic spectrum associated with ZIC1 variants: A neurodevelopmental disorder with and without craniosynostosis.Genetics in medicine : official journal of the American College of Medical Genetics · 2026
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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Anton V PersikovThe Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Joshua L WetzelThe Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA Department of Computer Science, Princeton University, Princeton, NJ 08544, USA.
Elizabeth F RowlandThe Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Benjamin L OakesThe Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Denise J XuThe Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Mona SinghThe Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA Department of Computer Science, Princeton University, Princeton, NJ 08544, USA mona@cs.princeton.edu.
Marcus B NoyesThe Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA mnoyes@princeton.edu.

Funding

Predicting and analyzing variation in cellular interactomesR01GM076275 · NIGMS · PRINCETON UNIVERSITY · PI SINGH, MONA · 2006 to 2022
$4.0M
NIGMS NIH HHS R01 GM076275
6 · The paper itself

Abstract

Cys2His2 zinc fingers (C2H2-ZFs) comprise the largest class of metazoan DNA-binding domains. Despite this domain's well-defined DNA-recognition interface, and its successful use in the design of chimeric proteins capable of targeting genomic regions of interest, much remains unknown about its DNA-binding landscape. To help bridge this gap in fundamental knowledge and to provide a resource for design-oriented applications, we screened large synthetic protein libraries to select binding C2H2-ZF domains for each possible three base pair target. The resulting data consist of >160 000 unique domain-DNA interactions and comprise the most comprehensive investigation of C2H2-ZF DNA-binding interactions to date. An integrated analysis of these independent screens yielded DNA-binding profiles for tens of thousands of domains and led to the successful design and prediction of C2H2-ZF DNA-binding specificities. Computational analyses uncovered important aspects of C2H2-ZF domain-DNA interactions, including the roles of within-finger context and domain position on base recognition. We observed the existence of numerous distinct binding strategies for each possible three base pair target and an apparent balance between affinity and specificity of binding. In sum, our comprehensive data help elucidate the complex binding landscape of C2H2-ZF domains and provide a foundation for efforts to determine, predict and engineer their DNA-binding specificities.

Indexed as

Zinc FingersBinding SitesCysteineData CollectionDNAHistidineCysteineDNAHistidine

Identifiers

PMID25593323
PMCPMC4330361

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Registered trials

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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.