Licensing of Centromeric Chromatin Assembly through the Mis18α-Mis18β Heterotetramer

Isaac K. Nardi, Ewelina Zasadzińska, Madison E. Stellfox, Christina M. Knippler, Daniel R. Foltz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Centromeres are specialized chromatin domains specified by the centromere-specific CENP-A nucleosome. The stable inheritance of vertebrate centromeres is an epigenetic process requiring deposition of new CENP-A nucleosomes by HJURP. We show HJURP is recruited to centromeres through a direct interaction between the HJURP centromere targeting domain and the Mis18α-β C-terminal coiled-coil domains. We demonstrate Mis18α and Mis18β form a heterotetramer through their C-terminal coiled-coil domains. Mis18α-β heterotetramer formation is required for Mis18BP1 binding and centromere recognition. S. pombe contains a single Mis18 isoform that forms a homotetramer, showing tetrameric Mis18 is conserved from fission yeast to humans. HJURP binding disrupts the Mis18α-β heterotetramer and removes Mis18α from centromeres. We propose stable binding of Mis18 to centromeres in telophase licenses them for CENP-A deposition. Binding of HJURP deposits CENP-A at centromeres and facilitates the removal of Mis18, restricting CENP-A deposition to a single event per cell cycle.

Original languageEnglish (US)
Pages (from-to)774-787
Number of pages14
JournalMolecular cell
Volume61
Issue number5
DOIs
StatePublished - Mar 3 2016

Keywords

  • Centromere
  • Chromatin
  • Mitosis
  • Nucleosome

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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