Decoding the Centromeric Nucleosome Through CENP-N

Overview

Journal Elife

Specialty Biology

Date 2017 Dec 28

PMID 29280735

Citations 68

Authors

Satyakrishna Pentakota

Keda Zhou

Charlotte Smith

Stefano Maffini

Arsen Petrovic

Garry P Morgan

John R Weir

Ingrid R Vetter

Andrea Musacchio

Karolin Luger

Affiliations

Soon will be listed here.

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.

Citing Articles

Non-nucleosomal (CENP-A/H4) - DNA complexes as a possible platform for centromere organization.

Ali-Ahmad A, Mors M, Carrer M, Li X, Bilokapic S, Halic M bioRxiv. 2025; .

PMID: 39803555 PMC: 11722257. DOI: 10.1101/2024.12.31.630874.

CENcyclopedia: Dynamic Landscape of Kinetochore Architecture Throughout the Cell Cycle.

Chen Y, Kilic E, Wang E, Rossman W, Suzuki A bioRxiv. 2024; .

PMID: 39677682 PMC: 11643120. DOI: 10.1101/2024.12.05.627000.

Histone variants: The bricks that fit differently.

Hegazy Y, Dhahri H, El Osmani N, George S, Chandler D, Fondufe-Mittendorf Y J Biol Chem. 2024; 301(1):108048.

PMID: 39638247 PMC: 11742582. DOI: 10.1016/j.jbc.2024.108048.

Characterization of Medusavirus encoded histones reveals nucleosome-like structures and a unique linker histone.

Toner C, Hoitsma N, Weerawarana S, Luger K Nat Commun. 2024; 15(1):9138.

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Vertebrate centromere architecture: from chromatin threads to functional structures.

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