Structural determinants for generating centromeric chromatin - PubMed (original) (raw)

. 2004 Jul 29;430(6999):578-82.

doi: 10.1038/nature02766.

Affiliations

• PMID: 15282608
• DOI: 10.1038/nature02766

Structural determinants for generating centromeric chromatin

Ben E Black et al. Nature. 2004.

Abstract

Mammalian centromeres are not defined by a consensus DNA sequence. In all eukaryotes a hallmark of functional centromeres--both normal ones and those formed aberrantly at atypical loci--is the accumulation of centromere protein A (CENP-A), a histone variant that replaces H3 in centromeric nucleosomes. Here we show using deuterium exchange/mass spectrometry coupled with hydrodynamic measures that CENP-A and histone H4 form sub-nucleosomal tetramers that are more compact and conformationally more rigid than the corresponding tetramers of histones H3 and H4. Substitution into histone H3 of the domain of CENP-A responsible for compaction is sufficient to direct it to centromeres. Thus, the centromere-targeting domain of CENP-A confers a unique structural rigidity to the nucleosomes into which it assembles, and is likely to have a role in maintaining centromere identity.

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