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Targeting Excessive EZH1 and EZH2 Activities for Abnormal Histone Methylation and Transcription Network in Malignant Lymphomas
http://hdl.handle.net/10659/00006672
http://hdl.handle.net/10659/00006672ece45f23-be55-42f7-a088-b12644f78a93
名前 / ファイル | ライセンス | アクション |
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R-2020-206_oosugi.pdf (7.1 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2020-11-18 | |||||
タイトル | ||||||
タイトル | Targeting Excessive EZH1 and EZH2 Activities for Abnormal Histone Methylation and Transcription Network in Malignant Lymphomas | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | EZH1 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | EZH2 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | H3K27me3 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | epigenetic drug | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | malignant lymphoma | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | adult T cell leukemia-lymphoma (ATL) | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | HTLV-1 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | polycomb | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | EZH1 | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | EZH2 | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | H3K27me3 | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | epigenetic drug | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | malignant lymphoma | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | adult T cell leukemia-lymphoma (ATL) | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | HTLV-1 | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | polycomb | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Yamagishi, Makoto
× Yamagishi, Makoto× Hori, Makoto× Fujikawa, Dai× Ohsugi, Takeo× Honma, Daisuke× Adachi, Nobuaki× Katano, Harutaka× Hishima, Tsunekazu× Kobayashi, Seiichiro× Nakano, Kazumi× Nakashima, Makoto× Iwanaga, Masako× Utsunomiya, Atae× Tanaka, Yuetsu× Okada, Seiji× Tsukasaki, Kunihiro× Tobinai, Kensei× Araki, Kazushi× Watanabe, Toshiki× Uchimaru, Kaoru |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Although global H3K27me3 reprogramming is a hallmark of cancer, no effective therapeutic strategy for H3K27me3-high malignancies harboring EZH2^<WT/WT> has yet been established. We explore epigenome and transcriptome in EZH2^<WT/WT> and EZH2^<WT/Mu> aggressive lymphomas and show that mutual interference and compensatory function of co-expressed EZH1 and EZH2 rearrange their own genome-wide distribution, thereby establishing restricted chromatin and gene expression signatures. Direct comparison of leading compounds introduces potency and a mechanism of action of the EZH1/2 dual inhibitor (valemetostat). The synthetic lethality is observed in all lymphoma models and primary adult T cell leukemia-lymphoma (ATL) cells. Opposing actions of EZH1/2-polycomb and SWI/SNF complexes are required for facultative heterochromatin formation. Inactivation of chromatin-associated genes (ARID1A, SMARCA4/BRG1, SMARCB1/SNF5, KDM6A/UTX, BAP1, KMT2D/MLL2) and oncovirus infection (HTLV-1, EBV) trigger EZH1/2 perturbation and H3K27me3 deposition. Our study provides the mechanism-based rationale for chemical dual targeting of EZH1/2 in cancer epigenome. | |||||
書誌情報 |
Cell Reports 巻 29, 号 8, p. 2321-2337, 発行日 2019-11 |
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ISBN | ||||||
識別子タイプ | ISBN | |||||
関連識別子 | 2211-1247 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1016/j.celrep.2019.10.083 | |||||
権利(URI) | ||||||
権利情報 | http://creativecommons.org/licenses/by-nc-nd/4.0/ | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
出版者 | ||||||
出版者 | Cell Press | |||||
資源タイプ | ||||||
内容記述タイプ | Other | |||||
内容記述 | Article |