Targeting Excessive EZH1 and EZH2 Activities for Abnormal Title Histone Methylation and Transcription Network in Malignant Lymphomas Yamagishi, Makoto; Hori, Makoto; Fujikawa, Dai; Ohsugi, Takeo; Honma, Daisuke; Adachi, Nobuaki; Katano, Harutaka; Hishima, Tsunekazu; Kobayashi, Seiichiro; Nakano, Kazumi; Author(s) Nakashima, Makoto; Iwanaga, Masako; Utsunomiya, Atae; Tanaka, Yuetsu; Okada, Seiji; Tsukasaki, Kunihiro; Tobinai, Kensei; Araki, Kazushi; Watanabe, Toshiki; Uchimaru, Kaoru Citation Cell reports, 29(8): 2321-2337 Issue Date 2019-11-19 URL http://hdl.handle.net/20.500.12000/45873 Creative Commons Attribution-NonCommercial- Rights NoDerivatives 4.0 Article Targeting Excessive EZH1 and EZH2 Activities for Abnormal Histone Methylation and Transcription Network in Malignant Lymphomas Graphical Abstract Authors Makoto Yamagishi, Makoto Hori, Dai Fujikawa, ..., Kazushi Araki, Toshiki Watanabe, Kaoru Uchimaru Correspondence
[email protected] (M.Y.),
[email protected] (K.U.) In Brief A mechanism-based, effective strategy for controlling oncogenic H3K27me3 remains an open question. Yamagishi et al. provide the scientific rationale for dual targeting of EZH1+EZH2 in malignancies overexpressing EZH2, such as ATL, PTCL, and DLBCL, or harboring mutations in histone-modifying genes, as well as in pre-cancerous cells epigenomically perturbed by oncovirus infection. Highlights d Lymphoma transcriptome is under control of global H3K27me3 accumulation WT/WT d EZH1 and EZH2 are druggable targets in EZH2 and EZH2WT/Mu malignancies d Inactivation of chromatin-associated genes triggers EZH1/2 perturbation d Targeting epigenome for pre-cancerous states is achieved by EZH1/2 inhibition Yamagishi et al., 2019, Cell Reports 29, 2321–2337 November 19, 2019 ª 2019 The Author(s).