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

Jun-Ichirou Ohzeki, Nobuaki Shono, Koichiro Otake, Nuno M C Martins, Kazuto Kugou, Hiroshi Kimura, Takahiro Nagase, Vladimir Larionov, William C Earnshaw, Hiroshi Masumoto

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)413-27
Number of pages15
JournalDevelopmental Cell
Volume37
Issue number5
DOIs
Publication statusPublished - 6 Jun 2016

Keywords

  • Centromere chromatin
  • heterochromatin
  • Alphoid DNA
  • CENP-A assembly
  • KAT7
  • histone acetylation
  • Suv39h1
  • histone methylation
  • Micronuclei formation
  • chromosome segregation

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