Unknown

Dataset Information

0

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


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.

SUBMITTER: Sekulic N 

PROVIDER: S-EPMC2946842 | BioStudies | 2010-01-01

REPOSITORIES: biostudies

Similar Datasets

2009-01-01 | S-EPMC2747366 | BioStudies
2012-01-01 | S-EPMC3353549 | BioStudies
1000-01-01 | S-EPMC3608502 | BioStudies
2013-01-01 | S-EPMC4418506 | BioStudies
1000-01-01 | S-EPMC2996678 | BioStudies
1000-01-01 | S-EPMC3730228 | BioStudies
1000-01-01 | S-EPMC4813710 | BioStudies
2016-01-01 | S-EPMC5097169 | BioStudies
1000-01-01 | S-EPMC5898018 | BioStudies
2011-01-01 | S-EPMC3207292 | BioStudies