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

Nishiyama, Akira; Dey, Anup; Miyazaki, Jun-ichi; Ozato, Keiko

doi:https://doi.org/10.1091/mbc.E05–08–0729

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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 Yet, when nocodazole was withdrawn, Brd4 was reloaded onto chromosomes, and cells proceeded to complete cell division.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

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Molecular Biology of the Cell. 2006, 17(2), p. 814-823
DC.title	Brd4 is required for recovery from Antimicrotubule Drug-induced Mitotic Arrest : Preservation of Acetylated Chromatin
DC.creator	Nishiyama, Akira
	Dey, Anup
	Miyazaki, Jun-ichi
	Ozato, Keiko
DC.publisher	The American Society for Cell Biology
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2006-02
DC.identifier	https://doi.org/10.1091/mbc.E05–08–0729
DCTERMS.abstract	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.
DC.rights	Copyright © 2006 by The American Society for Cell Biology
DC.format	application/pdf
citation_title	Brd4 is required for recovery from Antimicrotubule Drug-induced Mitotic Arrest : Preservation of Acetylated Chromatin
citation_author	Nishiyama, Akira
	Dey, Anup
	Miyazaki, Jun-ichi
	Ozato, Keiko
citation_publisher	The American Society for Cell Biology
citation_language	英語
citation_date	2006-02
citation_journal_title	Molecular Biology of the Cell
citation_volume	17
citation_issue	2
citation_firstpage	814
citation_lastpage	823
citation_doi	https://doi.org/10.1091/mbc.E05–08–0729
citation_public_url	https://hdl.handle.net/11094/23115

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