Decoding the centromeric nucleosome through CENP-N
- Max Planck Institute of Molecular Physiology, Germany
- University of Colorado, Boulder, United States
Abstract
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.
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Funding
H2020 European Research Council (AdG 669686)
- Andrea Musacchio
Deutsche Forschungsgemeinschaft (CRC1093)
- Andrea Musacchio
National Institutes of Health (GM067777)
- Karolin Luger
Howard Hughes Medical Institute
- Karolin Luger
Max-Planck-Gesellschaft (Open-access funding)
- Andrea Musacchio
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Pentakota et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Decoding the centromeric nucleosome through CENP-N
eLife 6:e33442.
https://doi.org/10.7554/eLife.33442
