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

Article

关键词: NUCLEOSOME CORE PARTICLE;    SMALL-ANGLE SCATTERING;    CENP-A NUCLEOSOMES;    ANGSTROM RESOLUTION;    CHROMATIN;    DNA;    HISTONES;    SYSTEM;    DOMAIN;    CRYSTALLOGRAPHY;   

DOI  :  10.1038/nature09323

来源: SCIE

【 摘 要 】

Centromeres are specified epigenetically, and the histone H3 variant CENP-A is assembled into the chromatin of all active centromeres(1). 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(3-6). Our results indicate that CENP-A marks centromere location by restructuring the nucleosome from within its folded histone core.

【 授权许可】

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