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Nature. 2010 Sep 16;467(7313):347-51. doi: 10.1038/nature09323. Epub 2010 Aug 25.

The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres.

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  • 1Department of Biochemistry and Biophysics, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104-6059, USA.

Abstract

Centromeres are specified epigenetically, and the histone H3 variant CENP-A is assembled into the chromatin of all active centromeres. Divergence from H3 raises the possibility that CENP-A generates unique chromatin features to mark physically centromere location. Here we report the crystal structure of a subnucleosomal heterotetramer, human (CENP-A-H4)(2), that reveals three distinguishing properties encoded by the residues that comprise the CENP-A targeting domain (CATD; ref. 2): (1) a CENP-A-CENP-A interface that is substantially rotated relative to the H3-H3 interface; (2) a protruding loop L1 of the opposite charge as that on H3; and (3) strong hydrophobic contacts that rigidify the CENP-A-H4 interface. Residues involved in the CENP-A-CENP-A rotation are required for efficient incorporation into centromeric chromatin, indicating specificity for an unconventional nucleosome shape. DNA topological analysis indicates that CENP-A-containing nucleosomes are octameric with conventional left-handed DNA wrapping, in contrast to other recent proposals. Our results indicate that CENP-A marks centromere location by restructuring the nucleosome from within its folded histone core.

PMID:
20739937
[PubMed - indexed for MEDLINE]
PMCID:
PMC2946842
Free PMC Article

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