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Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility
Nucleosomes, containing histone variants H2A.Z, are important for gene transcription initiation and termination, chromosome segregation and DNA double-strand break repair, among other functions. However, the underlying mechanisms of how H2A.Z influences nucleosome stability, dynamics and DNA accessi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9918499/ https://www.ncbi.nlm.nih.gov/pubmed/36765119 http://dx.doi.org/10.1038/s41467-023-36465-5 |
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author | Li, Shuxiang Wei, Tiejun Panchenko, Anna R. |
author_facet | Li, Shuxiang Wei, Tiejun Panchenko, Anna R. |
author_sort | Li, Shuxiang |
collection | PubMed |
description | Nucleosomes, containing histone variants H2A.Z, are important for gene transcription initiation and termination, chromosome segregation and DNA double-strand break repair, among other functions. However, the underlying mechanisms of how H2A.Z influences nucleosome stability, dynamics and DNA accessibility are not well understood, as experimental and computational evidence remains inconclusive. Our modeling efforts of human nucleosome stability and dynamics, along with comparisons with experimental data show that the incorporation of H2A.Z results in a substantial decrease of the energy barrier for DNA unwrapping. This leads to the spontaneous DNA unwrapping of about forty base pairs from both ends, nucleosome gapping and increased histone plasticity, which otherwise is not observed for canonical nucleosomes. We demonstrate that both N- and C-terminal tails of H2A.Z play major roles in these events, whereas the H3.3 variant exerts a negligible impact in modulating the DNA end unwrapping. In summary, our results indicate that H2A.Z deposition makes nucleosomes more mobile and DNA more accessible to transcriptional machinery and other chromatin components. |
format | Online Article Text |
id | pubmed-9918499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-99184992023-02-12 Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility Li, Shuxiang Wei, Tiejun Panchenko, Anna R. Nat Commun Article Nucleosomes, containing histone variants H2A.Z, are important for gene transcription initiation and termination, chromosome segregation and DNA double-strand break repair, among other functions. However, the underlying mechanisms of how H2A.Z influences nucleosome stability, dynamics and DNA accessibility are not well understood, as experimental and computational evidence remains inconclusive. Our modeling efforts of human nucleosome stability and dynamics, along with comparisons with experimental data show that the incorporation of H2A.Z results in a substantial decrease of the energy barrier for DNA unwrapping. This leads to the spontaneous DNA unwrapping of about forty base pairs from both ends, nucleosome gapping and increased histone plasticity, which otherwise is not observed for canonical nucleosomes. We demonstrate that both N- and C-terminal tails of H2A.Z play major roles in these events, whereas the H3.3 variant exerts a negligible impact in modulating the DNA end unwrapping. In summary, our results indicate that H2A.Z deposition makes nucleosomes more mobile and DNA more accessible to transcriptional machinery and other chromatin components. Nature Publishing Group UK 2023-02-11 /pmc/articles/PMC9918499/ /pubmed/36765119 http://dx.doi.org/10.1038/s41467-023-36465-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Li, Shuxiang Wei, Tiejun Panchenko, Anna R. Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility |
title | Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility |
title_full | Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility |
title_fullStr | Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility |
title_full_unstemmed | Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility |
title_short | Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility |
title_sort | histone variant h2a.z modulates nucleosome dynamics to promote dna accessibility |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9918499/ https://www.ncbi.nlm.nih.gov/pubmed/36765119 http://dx.doi.org/10.1038/s41467-023-36465-5 |
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