Licensing of Centromeric Chromatin Assembly through the Mis18α-Mis18β Heterotetramer

Mol Cell. 2016 Mar 3;61(5):774-787. doi: 10.1016/j.molcel.2016.02.014.


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.

Keywords: centromere; chromatin; mitosis; nucleosome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Autoantigens / genetics
  • Autoantigens / metabolism
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Centromere / metabolism*
  • Centromere Protein A
  • Chromatin Assembly and Disassembly*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Molecular Sequence Data
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Signal Transduction
  • Telophase*
  • Transfection


  • Adaptor Proteins, Signal Transducing
  • Autoantigens
  • CENPA protein, human
  • Cell Cycle Proteins
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • HJURP protein, human
  • MIS18A protein, human
  • OIP5 protein, human