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The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism
Centromeric nucleosomes are composed of the centromere-specific histone H3 variant CENP-A and the core histones H2A, H2B, and H4. To establish a functional kinetochore, histone H4 lysine-20 (H4K20) must be monomethylated, but the underlying mechanism has remained enigmatic. To provide structural ins...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362020/ https://www.ncbi.nlm.nih.gov/pubmed/30718488 http://dx.doi.org/10.1038/s41467-019-08314-x |
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author | Arimura, Yasuhiro Tachiwana, Hiroaki Takagi, Hiroki Hori, Tetsuya Kimura, Hiroshi Fukagawa, Tatsuo Kurumizaka, Hitoshi |
author_facet | Arimura, Yasuhiro Tachiwana, Hiroaki Takagi, Hiroki Hori, Tetsuya Kimura, Hiroshi Fukagawa, Tatsuo Kurumizaka, Hitoshi |
author_sort | Arimura, Yasuhiro |
collection | PubMed |
description | Centromeric nucleosomes are composed of the centromere-specific histone H3 variant CENP-A and the core histones H2A, H2B, and H4. To establish a functional kinetochore, histone H4 lysine-20 (H4K20) must be monomethylated, but the underlying mechanism has remained enigmatic. To provide structural insights into H4K20 methylation, we here solve the crystal structure of a nucleosome containing an H3.1-CENP-A chimera, H3.1(CATD), which has a CENP-A centromere targeting domain and preserves essential CENP-A functions in vivo. Compared to the canonical H3.1 nucleosome, the H3.1(CATD) nucleosome exhibits conformational changes in the H4 N-terminal tail leading to a relocation of H4K20. In particular, the H4 N-terminal tail interacts with glutamine-76 and aspartate-77 of canonical H3.1 while these interactions are cancelled in the presence of the CENP-A-specific residues valine-76 and lysine-77. Mutations of valine-76 and lysine-77 impair H4K20 monomethylation both in vitro and in vivo. These findings suggest that a CENP-A-mediated structural polymorphism may explain the preferential H4K20 monomethylation in centromeric nucleosomes. |
format | Online Article Text |
id | pubmed-6362020 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63620202019-02-06 The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism Arimura, Yasuhiro Tachiwana, Hiroaki Takagi, Hiroki Hori, Tetsuya Kimura, Hiroshi Fukagawa, Tatsuo Kurumizaka, Hitoshi Nat Commun Article Centromeric nucleosomes are composed of the centromere-specific histone H3 variant CENP-A and the core histones H2A, H2B, and H4. To establish a functional kinetochore, histone H4 lysine-20 (H4K20) must be monomethylated, but the underlying mechanism has remained enigmatic. To provide structural insights into H4K20 methylation, we here solve the crystal structure of a nucleosome containing an H3.1-CENP-A chimera, H3.1(CATD), which has a CENP-A centromere targeting domain and preserves essential CENP-A functions in vivo. Compared to the canonical H3.1 nucleosome, the H3.1(CATD) nucleosome exhibits conformational changes in the H4 N-terminal tail leading to a relocation of H4K20. In particular, the H4 N-terminal tail interacts with glutamine-76 and aspartate-77 of canonical H3.1 while these interactions are cancelled in the presence of the CENP-A-specific residues valine-76 and lysine-77. Mutations of valine-76 and lysine-77 impair H4K20 monomethylation both in vitro and in vivo. These findings suggest that a CENP-A-mediated structural polymorphism may explain the preferential H4K20 monomethylation in centromeric nucleosomes. Nature Publishing Group UK 2019-02-04 /pmc/articles/PMC6362020/ /pubmed/30718488 http://dx.doi.org/10.1038/s41467-019-08314-x Text en © The Author(s) 2019 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/. |
spellingShingle | Article Arimura, Yasuhiro Tachiwana, Hiroaki Takagi, Hiroki Hori, Tetsuya Kimura, Hiroshi Fukagawa, Tatsuo Kurumizaka, Hitoshi The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism |
title | The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism |
title_full | The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism |
title_fullStr | The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism |
title_full_unstemmed | The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism |
title_short | The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism |
title_sort | cenp-a centromere targeting domain facilitates h4k20 monomethylation in the nucleosome by structural polymorphism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362020/ https://www.ncbi.nlm.nih.gov/pubmed/30718488 http://dx.doi.org/10.1038/s41467-019-08314-x |
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