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Mutational processes in cancer preferentially affect binding of particular transcription factors
Protein binding microarrays provide comprehensive information about the DNA binding specificities of transcription factors (TFs), and can be used to quantitatively predict the effects of DNA sequence variation on TF binding. There has also been substantial progress in dissecting the patterns of muta...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870974/ https://www.ncbi.nlm.nih.gov/pubmed/33558557 http://dx.doi.org/10.1038/s41598-021-82910-0 |
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author | Liu, Mo Boot, Arnoud Ng, Alvin W. T. Gordân, Raluca Rozen, Steven G. |
author_facet | Liu, Mo Boot, Arnoud Ng, Alvin W. T. Gordân, Raluca Rozen, Steven G. |
author_sort | Liu, Mo |
collection | PubMed |
description | Protein binding microarrays provide comprehensive information about the DNA binding specificities of transcription factors (TFs), and can be used to quantitatively predict the effects of DNA sequence variation on TF binding. There has also been substantial progress in dissecting the patterns of mutations, i.e., the "mutational signatures", generated by different mutational processes. By combining these two layers of information we can investigate whether certain mutational processes tend to preferentially affect binding of particular classes of TFs. Such preferential alterations of binding might predispose to particular oncogenic pathways. We developed and implemented a method, termed "Signature-QBiC", that integrates protein binding microarray data with the signatures of mutational processes, with the aim of predicting which TFs’ binding profiles are preferentially perturbed by particular mutational processes. We used Signature-QBiC to predict the effects of 47 signatures of mutational processes on 582 human TFs. Pathway analysis showed that binding of TFs involved in NOTCH1 signaling is strongly affected by the signatures of several mutational processes, including exposure to ultraviolet radiation. Additionally, toll-like-receptor signaling pathways are also vulnerable to disruption by this exposure. This study provides a novel overview of the effects of mutational processes on TF binding and the potential of these processes to activate oncogenic pathways through mutating TF binding sites. |
format | Online Article Text |
id | pubmed-7870974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78709742021-02-10 Mutational processes in cancer preferentially affect binding of particular transcription factors Liu, Mo Boot, Arnoud Ng, Alvin W. T. Gordân, Raluca Rozen, Steven G. Sci Rep Article Protein binding microarrays provide comprehensive information about the DNA binding specificities of transcription factors (TFs), and can be used to quantitatively predict the effects of DNA sequence variation on TF binding. There has also been substantial progress in dissecting the patterns of mutations, i.e., the "mutational signatures", generated by different mutational processes. By combining these two layers of information we can investigate whether certain mutational processes tend to preferentially affect binding of particular classes of TFs. Such preferential alterations of binding might predispose to particular oncogenic pathways. We developed and implemented a method, termed "Signature-QBiC", that integrates protein binding microarray data with the signatures of mutational processes, with the aim of predicting which TFs’ binding profiles are preferentially perturbed by particular mutational processes. We used Signature-QBiC to predict the effects of 47 signatures of mutational processes on 582 human TFs. Pathway analysis showed that binding of TFs involved in NOTCH1 signaling is strongly affected by the signatures of several mutational processes, including exposure to ultraviolet radiation. Additionally, toll-like-receptor signaling pathways are also vulnerable to disruption by this exposure. This study provides a novel overview of the effects of mutational processes on TF binding and the potential of these processes to activate oncogenic pathways through mutating TF binding sites. Nature Publishing Group UK 2021-02-08 /pmc/articles/PMC7870974/ /pubmed/33558557 http://dx.doi.org/10.1038/s41598-021-82910-0 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Liu, Mo Boot, Arnoud Ng, Alvin W. T. Gordân, Raluca Rozen, Steven G. Mutational processes in cancer preferentially affect binding of particular transcription factors |
title | Mutational processes in cancer preferentially affect binding of particular transcription factors |
title_full | Mutational processes in cancer preferentially affect binding of particular transcription factors |
title_fullStr | Mutational processes in cancer preferentially affect binding of particular transcription factors |
title_full_unstemmed | Mutational processes in cancer preferentially affect binding of particular transcription factors |
title_short | Mutational processes in cancer preferentially affect binding of particular transcription factors |
title_sort | mutational processes in cancer preferentially affect binding of particular transcription factors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870974/ https://www.ncbi.nlm.nih.gov/pubmed/33558557 http://dx.doi.org/10.1038/s41598-021-82910-0 |
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