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

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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Ohzeki J,Shono N,Otake K,Martins NM,Kugou K,Kimura H,Nagase T,Larionov V,Earnshaw WC,Masumoto H

doi

10.1016/j.devcel.2016.05.006

subject

Has Abstract

pub_date

2016-06-06 00:00:00

pages

413-27

issue

5

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(16)30283-0

journal_volume

37

pub_type

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