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Specifically bound BZIP transcription factors modulate DNA supercoiling transitions

Torsional stress on DNA, introduced by molecular motors, constitutes an important regulatory mechanism of transcriptional control. Torsional stress can modulate specific binding of transcription factors to DNA and introduce local conformational changes that facilitate the opening of promoters and nu...

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Autores principales: Hörberg, Johanna, Reymer, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606469/
https://www.ncbi.nlm.nih.gov/pubmed/33139763
http://dx.doi.org/10.1038/s41598-020-75711-4
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author Hörberg, Johanna
Reymer, Anna
author_facet Hörberg, Johanna
Reymer, Anna
author_sort Hörberg, Johanna
collection PubMed
description Torsional stress on DNA, introduced by molecular motors, constitutes an important regulatory mechanism of transcriptional control. Torsional stress can modulate specific binding of transcription factors to DNA and introduce local conformational changes that facilitate the opening of promoters and nucleosome remodelling. Using all-atom microsecond scale molecular dynamics simulations together with a torsional restraint that controls the total twist of a DNA fragment, we address the impact of torsional stress on DNA complexation with a human BZIP transcription factor, MafB. We gradually over- and underwind DNA alone and in complex with MafB by 0.5° per dinucleotide step, starting from the relaxed state to a maximum of 5° per dinucleotide step, monitoring the evolution of the protein-DNA contacts at different degrees of torsional strain. Our computations show that MafB changes the DNA sequence-specific response to torsional stress. The dinucleotide steps that are susceptible to absorbing most of the torsional stress become more torsionally rigid, as they are involved in protein-DNA contacts. Also, the protein undergoes substantial conformational changes to follow the stress-induced DNA deformation, but mostly maintains the specific contacts with DNA. This results in a significant asymmetric increase of free energy of DNA twisting transitions, relative to free DNA, where overtwisting is more energetically unfavourable. Our data suggest that specifically bound BZIP factors could act as torsional stress insulators, modulating the propagation of torsional stress along the chromatin fibre, which might promote cooperative binding of collaborative DNA-binding factors.
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spelling pubmed-76064692020-11-03 Specifically bound BZIP transcription factors modulate DNA supercoiling transitions Hörberg, Johanna Reymer, Anna Sci Rep Article Torsional stress on DNA, introduced by molecular motors, constitutes an important regulatory mechanism of transcriptional control. Torsional stress can modulate specific binding of transcription factors to DNA and introduce local conformational changes that facilitate the opening of promoters and nucleosome remodelling. Using all-atom microsecond scale molecular dynamics simulations together with a torsional restraint that controls the total twist of a DNA fragment, we address the impact of torsional stress on DNA complexation with a human BZIP transcription factor, MafB. We gradually over- and underwind DNA alone and in complex with MafB by 0.5° per dinucleotide step, starting from the relaxed state to a maximum of 5° per dinucleotide step, monitoring the evolution of the protein-DNA contacts at different degrees of torsional strain. Our computations show that MafB changes the DNA sequence-specific response to torsional stress. The dinucleotide steps that are susceptible to absorbing most of the torsional stress become more torsionally rigid, as they are involved in protein-DNA contacts. Also, the protein undergoes substantial conformational changes to follow the stress-induced DNA deformation, but mostly maintains the specific contacts with DNA. This results in a significant asymmetric increase of free energy of DNA twisting transitions, relative to free DNA, where overtwisting is more energetically unfavourable. Our data suggest that specifically bound BZIP factors could act as torsional stress insulators, modulating the propagation of torsional stress along the chromatin fibre, which might promote cooperative binding of collaborative DNA-binding factors. Nature Publishing Group UK 2020-11-02 /pmc/articles/PMC7606469/ /pubmed/33139763 http://dx.doi.org/10.1038/s41598-020-75711-4 Text en © The Author(s) 2020 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
Hörberg, Johanna
Reymer, Anna
Specifically bound BZIP transcription factors modulate DNA supercoiling transitions
title Specifically bound BZIP transcription factors modulate DNA supercoiling transitions
title_full Specifically bound BZIP transcription factors modulate DNA supercoiling transitions
title_fullStr Specifically bound BZIP transcription factors modulate DNA supercoiling transitions
title_full_unstemmed Specifically bound BZIP transcription factors modulate DNA supercoiling transitions
title_short Specifically bound BZIP transcription factors modulate DNA supercoiling transitions
title_sort specifically bound bzip transcription factors modulate dna supercoiling transitions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606469/
https://www.ncbi.nlm.nih.gov/pubmed/33139763
http://dx.doi.org/10.1038/s41598-020-75711-4
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