2. Academic Validation
  3. KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation

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.
Jun-Ichirou Ohzeki 1,  Nobuaki Shono 1,  Koichiro Otake 1,  Nuno M C Martins 2,  Kazuto Kugou 1,  Hiroshi Kimura 3,  Takahiro Nagase 4,  Vladimir Larionov 5,  William C Earnshaw 2,  Hiroshi Masumoto 6
Affiliations

Affiliations

  • 1 Laboratory of Cell Engineering, Department of Frontier Research, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu 292-0818, Japan.
  • 2 Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, UK.
  • 3 Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
  • 4 Public Relations Team, Kazusa DNA Research Institute, Kisarazu 292-0818, Japan.
  • 5 Genome Structure and Function Group, Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • 6 Laboratory of Cell Engineering, Department of Frontier Research, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu 292-0818, Japan. Electronic address: masumoto@kazusa.or.jp.
PMID: 27270040 DOI: 10.1016/j.devcel.2016.05.006
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.

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