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

Meseguer, AlbertoÅrman, FilipFornés Crespo, Oriol, 1983-Molina Fernández, RubénBonet Martínez, Jaume, 1982-Fernández Fuentes, NarcísOliva Miguel, Baldomero2021-07-072021-07-072020Meseguer A, Årman F, Fornes O, Molina-Fernández R, Bonet J, Fernandez-Fuentes N, Oliva B. On the prediction of DNA-binding preferences of C2H2-ZF domains using structural models: application on human CTCF. NAR Genom Bioinform. 2020;2(3):lqaa046. DOI: 10.1093/nargab/lqaa0462631-9268http://hdl.handle.net/10230/48099Cis2-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.application/pdfeng© The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comOn the prediction of DNA-binding preferences of C2H2-ZF domains using structural models: application on human CTCFinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1093/nargab/lqaa046info:eu-repo/semantics/openAccess