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G-quadruplexes are transcription factor binding hubs in human chromatin
BACKGROUND: The binding of transcription factors (TF) to genomic targets is critical in the regulation of gene expression. Short, double-stranded DNA sequence motifs are routinely implicated in TF recruitment, but many questions remain on how binding site specificity is governed. RESULTS: Herein, we...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063395/ https://www.ncbi.nlm.nih.gov/pubmed/33892767 http://dx.doi.org/10.1186/s13059-021-02324-z |
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author | Spiegel, Jochen Cuesta, Sergio Martínez Adhikari, Santosh Hänsel-Hertsch, Robert Tannahill, David Balasubramanian, Shankar |
author_facet | Spiegel, Jochen Cuesta, Sergio Martínez Adhikari, Santosh Hänsel-Hertsch, Robert Tannahill, David Balasubramanian, Shankar |
author_sort | Spiegel, Jochen |
collection | PubMed |
description | BACKGROUND: The binding of transcription factors (TF) to genomic targets is critical in the regulation of gene expression. Short, double-stranded DNA sequence motifs are routinely implicated in TF recruitment, but many questions remain on how binding site specificity is governed. RESULTS: Herein, we reveal a previously unappreciated role for DNA secondary structures as key features for TF recruitment. In a systematic, genome-wide study, we discover that endogenous G-quadruplex secondary structures (G4s) are prevalent TF binding sites in human chromatin. Certain TFs bind G4s with affinities comparable to double-stranded DNA targets. We demonstrate that, in a chromatin context, this binding interaction is competed out with a small molecule. Notably, endogenous G4s are prominent binding sites for a large number of TFs, particularly at promoters of highly expressed genes. CONCLUSIONS: Our results reveal a novel non-canonical mechanism for TF binding whereby G4s operate as common binding hubs for many different TFs to promote increased transcription. |
format | Online Article Text |
id | pubmed-8063395 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-80633952021-04-23 G-quadruplexes are transcription factor binding hubs in human chromatin Spiegel, Jochen Cuesta, Sergio Martínez Adhikari, Santosh Hänsel-Hertsch, Robert Tannahill, David Balasubramanian, Shankar Genome Biol Research BACKGROUND: The binding of transcription factors (TF) to genomic targets is critical in the regulation of gene expression. Short, double-stranded DNA sequence motifs are routinely implicated in TF recruitment, but many questions remain on how binding site specificity is governed. RESULTS: Herein, we reveal a previously unappreciated role for DNA secondary structures as key features for TF recruitment. In a systematic, genome-wide study, we discover that endogenous G-quadruplex secondary structures (G4s) are prevalent TF binding sites in human chromatin. Certain TFs bind G4s with affinities comparable to double-stranded DNA targets. We demonstrate that, in a chromatin context, this binding interaction is competed out with a small molecule. Notably, endogenous G4s are prominent binding sites for a large number of TFs, particularly at promoters of highly expressed genes. CONCLUSIONS: Our results reveal a novel non-canonical mechanism for TF binding whereby G4s operate as common binding hubs for many different TFs to promote increased transcription. BioMed Central 2021-04-23 /pmc/articles/PMC8063395/ /pubmed/33892767 http://dx.doi.org/10.1186/s13059-021-02324-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Spiegel, Jochen Cuesta, Sergio Martínez Adhikari, Santosh Hänsel-Hertsch, Robert Tannahill, David Balasubramanian, Shankar G-quadruplexes are transcription factor binding hubs in human chromatin |
title | G-quadruplexes are transcription factor binding hubs in human chromatin |
title_full | G-quadruplexes are transcription factor binding hubs in human chromatin |
title_fullStr | G-quadruplexes are transcription factor binding hubs in human chromatin |
title_full_unstemmed | G-quadruplexes are transcription factor binding hubs in human chromatin |
title_short | G-quadruplexes are transcription factor binding hubs in human chromatin |
title_sort | g-quadruplexes are transcription factor binding hubs in human chromatin |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063395/ https://www.ncbi.nlm.nih.gov/pubmed/33892767 http://dx.doi.org/10.1186/s13059-021-02324-z |
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