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

doi:10.1016/j.devcel.2016.05.006

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

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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 language	English
Pages (from-to)	413-27
Number of pages	15
Journal	Developmental Cell
Volume	37
Issue number	5
DOIs	https://doi.org/10.1016/j.devcel.2016.05.006
Publication status	Published - 6 Jun 2016

Keywords / Materials (for Non-textual outputs)

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

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10.1016/j.devcel.2016.05.006

1-s2.0-S1534580716302830-mainFinal published version, 6.04 MB

The role of non-histone proteins in chromosome structure and function during mitosis
Earnshaw, B.
UK-based charities
1/01/11 → 30/09/16
Project: Research
The role of non-histone proteins in chromosome structure and function during mitosis and apoptosis
Earnshaw, B.
UK-based charities
1/10/05 → 30/09/15
Project: Research

Cite this

@article{8c05a372c3fc41c78aeb0e9e3f6fef75,

title = "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.",

keywords = "Centromere chromatin, heterochromatin, Alphoid DNA, CENP-A assembly, KAT7, histone acetylation, Suv39h1, histone methylation, Micronuclei formation, chromosome segregation",

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

year = "2016",

month = jun,

day = "6",

doi = "10.1016/j.devcel.2016.05.006",

language = "English",

volume = "37",

pages = "413--27",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation

AU - Ohzeki, Jun-Ichirou

AU - Shono, Nobuaki

AU - Otake, Koichiro

AU - Martins, Nuno M C

AU - Kugou, Kazuto

AU - Kimura, Hiroshi

AU - Nagase, Takahiro

AU - Larionov, Vladimir

AU - Earnshaw, William C

AU - Masumoto, Hiroshi

PY - 2016/6/6

Y1 - 2016/6/6

N2 - 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.

AB - 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.

KW - Centromere chromatin

KW - heterochromatin

KW - Alphoid DNA

KW - CENP-A assembly

KW - KAT7

KW - histone acetylation

KW - Suv39h1

KW - histone methylation

KW - Micronuclei formation

KW - chromosome segregation

U2 - 10.1016/j.devcel.2016.05.006

DO - 10.1016/j.devcel.2016.05.006

M3 - Article

C2 - 27270040

SN - 1534-5807

VL - 37

SP - 413

EP - 427

JO - Developmental Cell

JF - Developmental Cell

IS - 5

ER -

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

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Keywords / Materials (for Non-textual outputs)

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Projects

The role of non-histone proteins in chromosome structure and function during mitosis

The role of non-histone proteins in chromosome structure and function during mitosis and apoptosis

Cite this