We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The structure of (CENP-A-H4)<sub>2</sub> reveals physical features that mark centromeres.
- Authors
Sekulic, Nikolina; Bassett, Emily A.; Rogers, Danielle J.; Black, Ben E.
- 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.
- Publication
Nature, 2010, Vol 467, Issue 7313, p347
- ISSN
0028-0836
- Publication type
Academic Journal
- DOI
10.1038/nature09323