Cargando…
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...
Autores principales: | , |
---|---|
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 |
_version_ | 1783604487392329728 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7606469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT horbergjohanna specificallyboundbziptranscriptionfactorsmodulatednasupercoilingtransitions AT reymeranna specificallyboundbziptranscriptionfactorsmodulatednasupercoilingtransitions |