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Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity
Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes, including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuc...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449155/ https://www.ncbi.nlm.nih.gov/pubmed/28428255 http://dx.doi.org/10.1091/mbc.E16-11-0783 |
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author | Shimamoto, Yuta Tamura, Sachiko Masumoto, Hiroshi Maeshima, Kazuhiro |
author_facet | Shimamoto, Yuta Tamura, Sachiko Masumoto, Hiroshi Maeshima, Kazuhiro |
author_sort | Shimamoto, Yuta |
collection | PubMed |
description | Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes, including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We address this by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin. We find that the mechanical rigidity of nuclei depends on the continuity of the nucleosomal fiber and interactions between nucleosomes. Disrupting these chromatin features by varying cation concentration, acetylating histone tails, or digesting linker DNA results in loss of nuclear rigidity. In contrast, the levels of key chromatin assembly factors, including cohesin, condensin II, and CTCF, and a major nuclear envelope protein, lamin, are unaffected. Together with in situ evidence using living cells and a simple mechanical model, our findings reveal a chromatin-based regulation of the nuclear mechanical response and provide insight into the significance of local and global chromatin structures, such as those associated with interdigitated or melted nucleosomal fibers. |
format | Online Article Text |
id | pubmed-5449155 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-54491552017-08-16 Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity Shimamoto, Yuta Tamura, Sachiko Masumoto, Hiroshi Maeshima, Kazuhiro Mol Biol Cell Articles Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes, including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We address this by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin. We find that the mechanical rigidity of nuclei depends on the continuity of the nucleosomal fiber and interactions between nucleosomes. Disrupting these chromatin features by varying cation concentration, acetylating histone tails, or digesting linker DNA results in loss of nuclear rigidity. In contrast, the levels of key chromatin assembly factors, including cohesin, condensin II, and CTCF, and a major nuclear envelope protein, lamin, are unaffected. Together with in situ evidence using living cells and a simple mechanical model, our findings reveal a chromatin-based regulation of the nuclear mechanical response and provide insight into the significance of local and global chromatin structures, such as those associated with interdigitated or melted nucleosomal fibers. The American Society for Cell Biology 2017-06-01 /pmc/articles/PMC5449155/ /pubmed/28428255 http://dx.doi.org/10.1091/mbc.E16-11-0783 Text en © 2017 Shimamoto et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Shimamoto, Yuta Tamura, Sachiko Masumoto, Hiroshi Maeshima, Kazuhiro Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity |
title | Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity |
title_full | Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity |
title_fullStr | Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity |
title_full_unstemmed | Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity |
title_short | Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity |
title_sort | nucleosome–nucleosome interactions via histone tails and linker dna regulate nuclear rigidity |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449155/ https://www.ncbi.nlm.nih.gov/pubmed/28428255 http://dx.doi.org/10.1091/mbc.E16-11-0783 |
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