KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation

Dev Cell. 2016 Jun 6;37(5):413-27. doi: 10.1016/j.devcel.2016.05.006.


Centromere chromatin containing histone H3 variant CENP-A is required for accurate chromosome segregation as a foundation for kinetochore assembly. Human centromere chromatin assembles on a part of the long α-satellite (alphoid) DNA array, where it is flanked by pericentric heterochromatin. Heterochromatin spreads into adjacent chromatin and represses gene expression, and it can antagonize centromere function or CENP-A assembly. Here, we demonstrate an interaction between CENP-A assembly factor M18BP1 and acetyltransferase KAT7/HBO1/MYST2. Knocking out KAT7 in HeLa cells reduced centromeric CENP-A assembly. Mitotic chromosome misalignment and micronuclei formation increased in the knockout cells and were enhanced when the histone H3-K9 trimethylase Suv39h1 was overproduced. Tethering KAT7 to an ectopic alphoid DNA integration site removed heterochromatic H3K9me3 modification and was sufficient to stimulate new CENP-A or histone H3.3 assembly. Thus, KAT7-containing acetyltransferases associating with the Mis18 complex provides competence for histone turnover/exchange activity on alphoid DNA and prevents Suv39h1-mediated heterochromatin invasion into centromeres.

MeSH terms

  • Autoantigens / metabolism*
  • Centromere / metabolism*
  • Centromere Protein A
  • Chromatin Assembly and Disassembly*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Segregation
  • DNA-Binding Proteins / metabolism
  • G1 Phase
  • Gene Knockout Techniques
  • HeLa Cells
  • Histone Acetyltransferases / metabolism*
  • Histones / metabolism
  • Humans
  • Lysine / metabolism
  • Methylation
  • Methyltransferases / metabolism*
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / metabolism
  • Protein Stability
  • Protein Subunits / metabolism
  • Repressor Proteins / metabolism*
  • Trans-Activators / metabolism


  • Autoantigens
  • CENPA protein, human
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • HJURP protein, human
  • Histones
  • Multiprotein Complexes
  • Nuclear Proteins
  • Protein Subunits
  • RSF1 protein, human
  • Repressor Proteins
  • Trans-Activators
  • SUV39H1 protein, human
  • Methyltransferases
  • Histone Acetyltransferases
  • KAT7 protein, human
  • Lysine