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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...

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Autores principales: Shimamoto, Yuta, Tamura, Sachiko, Masumoto, Hiroshi, Maeshima, Kazuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
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.
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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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