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

EMBO J. 2013 Jul 31;32(15):2113-24. doi: 10.1038/emboj.2013.142. Epub 2013 Jun 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Centromere / genetics
  • Centromere / metabolism*
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*
  • Protein Multimerization / physiology*
  • Protein Structure, Tertiary


  • Autoantigens
  • CENPA protein, human
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • HJURP protein, human
  • Histones
  • Nucleosomes