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Structural determinants for generating centromeric chromatin

Ben E. Black, Daniel R. Foltz, Srinivas Chakravarthy, Karolin Luger, Virgil L. Woods () and Don W. Cleveland ()
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Ben E. Black: University of California
Daniel R. Foltz: University of California
Srinivas Chakravarthy: Colorado State University
Karolin Luger: Colorado State University
Virgil L. Woods: University of California
Don W. Cleveland: University of California

Nature, 2004, vol. 430, issue 6999, 578-582

Abstract: 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 nucleosomes1,2,3,4,5,6,7. 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.

Date: 2004
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DOI: 10.1038/nature02766

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