Brd4 is required for recovery from Antimicrotubule Drug-induced Mitotic Arrest : Preservation of Acetylated Chromatin

Nishiyama, Akira; Dey, Anup; Miyazaki, Jun-ichi et al.

Molecular Biology of the Cell, 2006, 17(2), 814-823

アクセス数:156件（2025-05-11 23:32 集計）

固定URL: https://hdl.handle.net/11094/23115

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タイトル
Brd4 is required for recovery from Antimicrotubule Drug-induced Mitotic Arrest : Preservation of Acetylated Chromatin
著者
NRID
1000080589664 1000080589664
著者名
Nishiyama, Akira
著者名
Dey, Anup
NRID
1000080229830 1000080229830
著者名
Miyazaki, Jun-ichi
著者名
Ozato, Keiko
抄録
The mammalian bromodomain protein Brd4 interacts with mitotic chromosomes by binding to acetylated histone H3 and H4 and is thought to play a role in epigenetic memory. Mitotic cells are susceptible to antimicrotubule drugs. These drugs activate multiple response pathways and arrest cells at mitosis. We found that Brd4 was rapidly released from chromosomes upon treatment with antimicrotubule drugs, including the reversible agent nocodazole. Yet, when nocodazole was withdrawn, Brd4 was reloaded onto chromosomes, and cells proceeded to complete cell division. However, cells in which a Brd4 allele was disrupted (Brd4+/-), and expressing only half of the normal Brd4 levels, were defective in reloading Brd4 onto chromosomes. Consequently, Brd4+/- cells were impaired in their ability to recover from nocodazole-induced mitotic arrest: a large fraction of +/- cells failed to reach anaphase after drug withdrawal, and those that entered anaphase showed an increased frequency of abnormal chromosomal segregation. The reloading defect observed in Brd4+/- cells coincided with selective hypoacetylation of lysine residues on H3 and H4. The histone deacetylase inhibitor trichostatin A increased global histone acetylation and perturbed nocodazole-induced Brd4 unloading. Brd4 plays an integral part in a cellular response to drug-induced mitotic stress by preserving a properly acetylated chromatin status.
出版者
The American Society for Cell Biology
収録物名
Molecular Biology of the Cell
巻(号)
17(2)
ページ
814-823
刊行年月
2006-02
言語
英語
ハンドルURL
https://hdl.handle.net/11094/23115
PISSN
10591524
NCID
AA10830484
関連情報 (isIdenticalTo)
DOI (出版社版)
https://doi.org/10.1091/mbc.E05–08–0729
アクセス権
open access
権利情報
Copyright © 2006 by The American Society for Cell Biology
出版タイプ
Version of Record
カテゴリ
学術雑誌論文 Journal Article