On the prediction of DNA-binding preferences of C2H2-ZF domains using structural models: application on human CTCF. Issue 3 (1st July 2020)

• Record Type: Journal Article
• Authors: Meseguer, Alberto; Årman, Filip; Fornes, Oriol; Molina-Fernández, Ruben; Bonet, Jaume; Fernandez-Fuentes, Narcis; Oliva, Baldo
• Is Part Of: NAR genomics and bioinformatics. Volume 2:Issue 3(2020)
• Publication Date: 2020-07-01
• Subjects: Genomics -- Periodicals; Bioinformatics -- Periodicals; 572.8
• DOI: 10.1093/nargab/lqaa046
• Languages: English
• ISSNs: 2631-9268

Abstract

Abstract: 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.