HJURP is involved in the expansion of centromeric chromatin

Mol Biol Cell. 2015 Aug 1;26(15):2742-54. doi: 10.1091/mbc.E15-02-0094. Epub 2015 Jun 10.

Abstract

The CENP-A-specific chaperone HJURP mediates CENP-A deposition at centromeres. The N-terminal region of HJURP is responsible for binding to soluble CENP-A. However, it is unclear whether other regions of HJURP have additional functions for centromere formation and maintenance. In this study, we generated chicken DT40 knockout cell lines and gene replacement constructs for HJURP to assess the additional functions of HJURP in vivo. Our analysis revealed that the middle region of HJURP associates with the Mis18 complex protein M18BP1/KNL2 and that the HJURP-M18BP1 association is required for HJURP function. In addition, on the basis of the analysis of artificial centromeres induced by ectopic HJURP localization, we demonstrate that HJURP exhibits a centromere expansion activity that is separable from its CENP-A-binding activity. We also observed centromere expansion surrounding natural centromeres after HJURP overexpression. We propose that this centromere expansion activity reflects the functional properties of HJURP, which uses this activity to contribute to the plastic establishment of a centromeric chromatin structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / metabolism
  • Cell Line
  • Centromere / metabolism*
  • Centromere Protein A
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins / metabolism*
  • Histones / metabolism
  • Humans
  • Molecular Chaperones
  • Protein Structure, Tertiary

Substances

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