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PubMed · 15282608

Structural determinants for generating centromeric chromatin.

Ben E Black·Daniel R Foltz·Srinivas Chakravarthy·Karolin Luger·Virgil L Woods·Don W Cleveland
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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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Amino Acid SequenceAutoantigensBinding SitesCell Line, TumorCentromereCentromere Protein AChromatinChromosomal Proteins, Non-HistoneDeuterium Exchange MeasurementHistonesHumansModels, MolecularMolecular Sequence DataNucleic Acid ConformationNucleosomesProtein Structure, QuaternaryProtein Structure, TertiaryJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Ben E Black, Daniel R Foltz, Srinivas Chakravarthy, Karolin Luger, Virgil L Woods, Don W Cleveland. 2004-07-29. Structural determinants for generating centromeric chromatin.. https://doi.org/10.1038/nature02766

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