Global analysis of core histones reveals nucleosomal surfaces required for chromosome bi-orientation

Satoshi Kawashima, Yu Nakabayashi, Kazuko Matsubara, Norihiko Sano, Takemi Enomoto, Kozo Tanaka, Masayuki Seki, Masami Horikoshi

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


The attachment of sister kinetochores to microtubules from opposite spindle poles is essential for faithful chromosome segregation. Kinetochore assembly requires centromere-specific nucleosomes containing the histone H3 variant CenH3. However, the functional roles of the canonical histones (H2A, H2B, H3, and H4) in chromosome segregation remain elusive. Using a library of histone point mutants in Saccharomyces cerevisiae, 24 histone residues that conferred sensitivity to the microtubule-depolymerizing drugs thiabendazole (TBZ) and benomyl were identified. Twenty-three of these mutations were clustered at three spatially separated nucleosomal regions designated TBS-I,-II, and-III (TBZ/benomyl-sensitive regions I-III). Elevation of mono-polar attachment induced by prior nocodazole treatment was observed in H2A-I112A (TBS-I), H2A-E57A (TBS-II), and H4-L97A (TBS-III) cells. Severe impairment of the centromere localization of Sgo1, a key modulator of chromosome bi-orientation, occurred in H2A-I112A and H2A-E57A cells. In addition, the pericentromeric localization of Htz1, the histone H2A variant, was impaired in H4-L97A cells. These results suggest that the spatially separated nucleosomal regions, TBS-I and-II, are necessary for Sgo1-mediated chromosome bi-orientation and that TBS-III is required for Htz1 function.

Original languageEnglish
Pages (from-to)3353-3367
Number of pages15
JournalEMBO Journal
Issue number16
Publication statusPublished - 2011 Aug 17


  • CPC; histone
  • microtubule-depolymerizing drug
  • nucleosome
  • Sgo1


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