On the prediction of DNA-binding preferences of C2H2-ZF domains using structural models: application on human CTCF.


Journal

NAR genomics and bioinformatics
ISSN: 2631-9268
Titre abrégé: NAR Genom Bioinform
Pays: England
ID NLM: 101756213

Informations de publication

Date de publication:
Sep 2020
Historique:
received: 13 01 2020
revised: 07 05 2020
accepted: 10 06 2020
entrez: 12 2 2021
pubmed: 13 2 2021
medline: 13 2 2021
Statut: epublish

Résumé

Cis2-His2 zinc finger (C2H2-ZF) proteins are the largest family of transcription factors in human and higher metazoans. To date, the DNA-binding preferences of many members of this family remain unknown. We have developed a computational method to predict their DNA-binding preferences. We have computed theoretical position weight matrices (PWMs) of proteins composed by C2H2-ZF domains, with the only requirement of an input structure. We have predicted more than two-third of a single zinc-finger domain binding site for about 70% variants of Zif268, a classical member of this family. We have successfully matched between 60 and 90% of the binding-site motif of examples of proteins composed by three C2H2-ZF domains in JASPAR, a standard database of PWMs. The tests are used as a proof of the capacity to scan a DNA fragment and find the potential binding sites of transcription-factors formed by C2H2-ZF domains. As an example, we have tested the approach to predict the DNA-binding preferences of the human chromatin binding factor CTCF. We offer a server to model the structure of a zinc-finger protein and predict its PWM.

Identifiants

pubmed: 33575598
doi: 10.1093/nargab/lqaa046
pii: lqaa046
pmc: PMC7671317
doi:

Types de publication

Journal Article

Langues

eng

Pagination

lqaa046

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.

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Auteurs

Alberto Meseguer (A)

Structural Bioinformatics Lab (GRIB-IMIM), Department of Experimental and Health Science, University Pompeu Fabra, Barcelona, Catalonia 08005, Spain.

Filip Årman (F)

Structural Bioinformatics Lab (GRIB-IMIM), Department of Experimental and Health Science, University Pompeu Fabra, Barcelona, Catalonia 08005, Spain.

Oriol Fornes (O)

Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.

Ruben Molina-Fernández (R)

Structural Bioinformatics Lab (GRIB-IMIM), Department of Experimental and Health Science, University Pompeu Fabra, Barcelona, Catalonia 08005, Spain.

Jaume Bonet (J)

Laboratory of Protein Design & Immunoengineering, School of Engineering, Ecole Polytechnique Federale de Lausanne, Lausanne 1015, Vaud, Switzerland.

Narcis Fernandez-Fuentes (N)

Department of Biosciences, U Science Tech, Universitat de Vic-Universitat Central de Catalunya, Vic, Catalonia 08500, Spain.

Baldo Oliva (B)

Structural Bioinformatics Lab (GRIB-IMIM), Department of Experimental and Health Science, University Pompeu Fabra, Barcelona, Catalonia 08005, Spain.

Classifications MeSH