The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism
| Autor: | Arimura, Y., Tachiwana, H., Takagi, H., Hori, T., Kimura, Hiroshi, Fukagawa, T., Kurumizaka, H. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Mutation/genetics Centromere/genetics/*metabolism Science Nucleosomes/genetics/*metabolism Blotting Western Centromere General Physics and Astronomy 02 engineering and technology macromolecular substances Methylation General Biochemistry Genetics and Molecular Biology Article Cell Line Histone H4 Centromere Protein A/genetics/*metabolism 03 medical and health sciences Histone H3 Chimera (genetics) Nucleosome Animals Humans Polymorphism Genetic/genetics lcsh:Science Multidisciplinary Polymorphism Genetic biology Chemistry Kinetochore General Chemistry 021001 nanoscience & nanotechnology Cell biology Nucleosomes 030104 developmental biology Histone Mutation biology.protein lcsh:Q 0210 nano-technology Chickens Centromere Protein A |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-10 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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, H3.1CATD, which has a CENP-A centromere targeting domain and preserves essential CENP-A functions in vivo. Compared to the canonical H3.1 nucleosome, the H3.1CATD 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. Kinetochore function depends on H4K20 monomethylation in centromeric nucleosomes but the underlying mechanism is unclear. Here, the authors provide evidence that the centromere-specific nucleosome subunit CENP-A facilitates H4K20 methylation by enabling a conformational change of the H4 N-terminal tail. |
| Databáze: | OpenAIRE |
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