Molecular Biology

The Sign of Four

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Science  24 Aug 2007:
Vol. 317, Issue 5841, pp. 1010
DOI: 10.1126/science.317.5841.1010b

Nucleosomes constitute the principal structural motif of eukaryotic chromosomes and contain octomers of highly conserved histones with the almost invariant stoichiometry of two copies each of H2A, H2B, H3, and H4. Centromeres are specialized regions within chromosomes that play a critical role in the accurate segregation of duplicated chromosomes during cell division. Centromere nucleosomes contain an alternative histone, CenH3, which is thought to define centromere identity and participate in mitotic mechanics.

Dalal et al. have explored these issues through a biochemical and biophysical analysis of centromere nucleosomes in Drosophila. Cross-linking of bulk chromatin from crude extracts and within purified nuclei revealed that CenH3 appears in a heterotypic tetrameric half-sized nucleosome, with one copy each of CenH3, H2A, H2B, and H4. This composition was confirmed by mass spectrometry, and atomic force microscopy showed tetramers to be half the height of octomers. The tetramers protect less DNA [~120 base pairs (bp)] than the canonical octomers (~150 bp) and do not seem to form as regular higher-order structures as the octomer, yielding longer and more variable DNA linker lengths. This looser chromatin conformation, embedded within heterochromatin, may be critical for tethering the kinetochore to the centromere. — GR

PLoS Biol. 5, e218 (2007).

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