Dimerization of the CENP-A assembly factor HJURP is required for centromeric nucleosome deposition

Ewelina Zasadzińska, Meghan C. Barnhart-Dailey, P. Henning J L Kuich, Daniel R. Foltz*

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

The epigenetic mark of the centromere is thought to be a unique centromeric nucleosome that contains the histone H3 variant, centromere protein-A (CENP-A). The deposition of new centromeric nucleosomes requires the CENP-A-specific chromatin assembly factor HJURP (Holliday junction recognition protein). Crystallographic and biochemical data demonstrate that the Scm3-like domain of HJURP binds a single CENP-A-histone H4 heterodimer. However, several lines of evidence suggest that HJURP forms an octameric CENP-A nucleosome. How an octameric CENP-A nucleosome forms from individual CENP-A/histone H4 heterodimers is unknown. Here, we show that HJURP forms a homodimer through its C-terminal domain that includes the second HJURP-C domain. HJURP exists as a dimer in the soluble preassembly complex and at chromatin when new CENP-A is deposited. Dimerization of HJURP is essential for the deposition of new CENP-A nucleosomes. The recruitment of HJURP to centromeres occurs independent of dimerization and CENP-A binding. These data provide a mechanism whereby the CENP-A pre-nucleosomal complex achieves assembly of the octameric CENP-A nucleosome through the dimerization of the CENP-A chaperone HJURP.

Original languageEnglish (US)
Pages (from-to)2113-2124
Number of pages12
JournalEMBO Journal
Volume32
Issue number15
DOIs
StatePublished - Jul 31 2013

Keywords

  • CENP-A
  • centromere
  • chromatin
  • mitosis
  • nucleosome

ASJC Scopus subject areas

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

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