Licensing of Centromeric Chromatin Assembly through the Mis18α-Mis18β Heterotetramer
- Resource Type
- Authors
- Isaac K. Nardi; Madison E. Stellfox; Daniel R. Foltz; Christina M. Knippler; Ewelina Zasadzińska
- Source
- Molecular Cell. 61(5):774-787
- Subject
- 0301 basic medicine
Chromosomal Proteins, Non-Histone
Centromere
Molecular Sequence Data
Cell Cycle Proteins
macromolecular substances
Biology
Transfection
DNA-binding protein
Autoantigens
Article
03 medical and health sciences
Cell Line, Tumor
Nucleosome
Humans
Protein Interaction Domains and Motifs
Amino Acid Sequence
Telophase
Mitosis
Molecular Biology
Adaptor Proteins, Signal Transducing
Genetics
Cell Biology
Chromatin Assembly and Disassembly
Heterotetramer
Chromatin
Cell biology
DNA-Binding Proteins
030104 developmental biology
Protein Multimerization
Centromere Protein A
Homotetramer
Protein Binding
Signal Transduction
- Language
- ISSN
- 1097-2765
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.