Decoding the centromeric nucleosome through CENP-N
Centromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/33442 |
| _version_ | 1828375300958846976 |
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| author | Satyakrishna Pentakota Keda Zhou Charlotte Smith Stefano Maffini Arsen Petrovic Garry P Morgan John R Weir Ingrid R Vetter Andrea Musacchio Karolin Luger |
| author_facet | Satyakrishna Pentakota Keda Zhou Charlotte Smith Stefano Maffini Arsen Petrovic Garry P Morgan John R Weir Ingrid R Vetter Andrea Musacchio Karolin Luger |
| author_sort | Satyakrishna Pentakota |
| collection | DOAJ |
| description | Centromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP-C and CENP-N, recognize CENP-A in the context of a rare CENP-A nucleosome. Here, we reveal the structural basis for the exquisite selectivity of CENP-N for centromeres. CENP-N uses charge and space complementarity to decode the L1 loop that is unique to CENP-A. It also engages in extensive interactions with a 15-base pair segment of the distorted nucleosomal DNA double helix, in a position predicted to exclude chromatin remodelling enzymes. Besides CENP-A, stable centromere recruitment of CENP-N requires a coincident interaction with a newly identified binding motif on nucleosome-bound CENP-C. Collectively, our studies clarify how CENP-N and CENP-C decode and stabilize the non-canonical CENP-A nucleosome to enforce epigenetic centromere specification and kinetochore assembly. |
| first_indexed | 2024-04-14T07:45:29Z |
| format | Article |
| id | doaj.art-c10118af6b92425bb5254d424be03270 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:45:29Z |
| publishDate | 2017-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c10118af6b92425bb5254d424be032702022-12-22T02:05:22ZengeLife Sciences Publications LtdeLife2050-084X2017-12-01610.7554/eLife.33442Decoding the centromeric nucleosome through CENP-NSatyakrishna Pentakota0Keda Zhou1https://orcid.org/0000-0003-0258-1489Charlotte Smith2Stefano Maffini3Arsen Petrovic4Garry P Morgan5John R Weir6Ingrid R Vetter7Andrea Musacchio8https://orcid.org/0000-0003-2362-8784Karolin Luger9https://orcid.org/0000-0001-5136-5331Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, GermanyDepartment of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, United StatesDepartment of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, GermanyDepartment of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, GermanyDepartment of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, GermanyDepartment of MCDB, University of Colorado at Boulder, Boulder, United StatesDepartment of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, GermanyDepartment of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, GermanyDepartment of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany; Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, GermanyDepartment of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, United States; Howard Hughes Medical Institute, Maryland, United StatesCentromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP-C and CENP-N, recognize CENP-A in the context of a rare CENP-A nucleosome. Here, we reveal the structural basis for the exquisite selectivity of CENP-N for centromeres. CENP-N uses charge and space complementarity to decode the L1 loop that is unique to CENP-A. It also engages in extensive interactions with a 15-base pair segment of the distorted nucleosomal DNA double helix, in a position predicted to exclude chromatin remodelling enzymes. Besides CENP-A, stable centromere recruitment of CENP-N requires a coincident interaction with a newly identified binding motif on nucleosome-bound CENP-C. Collectively, our studies clarify how CENP-N and CENP-C decode and stabilize the non-canonical CENP-A nucleosome to enforce epigenetic centromere specification and kinetochore assembly.https://elifesciences.org/articles/33442centromerekinetochoreCENP-ACENP-NCENP-Cmitosis |
| spellingShingle | Satyakrishna Pentakota Keda Zhou Charlotte Smith Stefano Maffini Arsen Petrovic Garry P Morgan John R Weir Ingrid R Vetter Andrea Musacchio Karolin Luger Decoding the centromeric nucleosome through CENP-N eLife centromere kinetochore CENP-A CENP-N CENP-C mitosis |
| title | Decoding the centromeric nucleosome through CENP-N |
| title_full | Decoding the centromeric nucleosome through CENP-N |
| title_fullStr | Decoding the centromeric nucleosome through CENP-N |
| title_full_unstemmed | Decoding the centromeric nucleosome through CENP-N |
| title_short | Decoding the centromeric nucleosome through CENP-N |
| title_sort | decoding the centromeric nucleosome through cenp n |
| topic | centromere kinetochore CENP-A CENP-N CENP-C mitosis |
| url | https://elifesciences.org/articles/33442 |
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