The kinetochore module Okp1 CENP-Q /Ame1 CENP-U is a reader for N-terminal modifications on the centromeric histone Cse4 CENP-A

Ekaterina A. Anedchenko, Anke Samel-Pommerencke, Tra My Tran Nguyen, Sara Shahnejat-Bushehri, Juliane Pöpsel, Daniel Lauster, Andreas Herrmann, Juri Rappsilber, Alessandro Cuomo, Tiziana Bonaldi, Ann E. Ehrenhofer-Murray

Research output: Contribution to journalArticle

Abstract

Kinetochores are supramolecular assemblies that link centromeres to microtubules for sister chromatid segregation in mitosis. For this, the inner kinetochore CCAN/Ctf19 complex binds to centromeric chromatin containing the histone variant CENP-A, but whether the interaction of kinetochore components to centromeric nucleosomes is regulated by posttranslational modifications is unknown. Here, we investigated how methylation of arginine 37 (R37Me) and acetylation of lysine 49 (K49Ac) on the CENP-A homolog Cse4 from Saccharomyces cerevisiae regulate molecular interactions at the inner kinetochore. Importantly, we found that the Cse4 N-terminus binds with high affinity to the Ctf19 complex subassembly Okp1/Ame1 (CENP-Q/CENP-U in higher eukaryotes), and that this interaction is inhibited by R37Me and K49Ac modification on Cse4. In vivo defects in cse4-R37A were suppressed by mutations in OKP1 and AME1, and biochemical analysis of a mutant version of Okp1 showed increased affinity for Cse4. Altogether, our results demonstrate that the Okp1/Ame1 heterodimer is a reader module for posttranslational modifications on Cse4, thereby targeting the yeast CCAN complex to centromeric chromatin.

Original languageEnglish
Article numbere98991
JournalEMBO Journal
Volume38
Issue number1
DOIs
Publication statusPublished - Jan 3 2019

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Keywords

  • Ame1
  • centromere
  • Gcn5
  • Okp1
  • posttranslational modification

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Anedchenko, E. A., Samel-Pommerencke, A., Tran Nguyen, T. M., Shahnejat-Bushehri, S., Pöpsel, J., Lauster, D., Herrmann, A., Rappsilber, J., Cuomo, A., Bonaldi, T., & Ehrenhofer-Murray, A. E. (2019). The kinetochore module Okp1 CENP-Q /Ame1 CENP-U is a reader for N-terminal modifications on the centromeric histone Cse4 CENP-A. EMBO Journal, 38(1), [e98991]. https://doi.org/10.15252/embj.201898991