title: EED regulates epithelial-mesenchymal transition of cancer cells induced by TGF-β.
abstract: Histone methylation is involved in various biological and pathological processes including cancer development. In this study, we found that EED, a component of Polycomb repressive complex-2 (PRC2) that catalyzes methylation of lysine 27 of histone H3 (H3K27), was involved in epithelial-mesenchymal transition (EMT) of cancer cells induced by Transforming Growth Factor-beta (TGF-β). The expression of EED was increased during TGF-β-induced EMT and knockdown of EED inhibited TGF-β-induced morphological conversion of the cells associated with EMT. EED knockdown antagonized TGF-β-dependent expression changes of EMT-related genes such as CDH1, ZEB1, ZEB2 and microRNA-200 (miR-200) family. Chromatin immunoprecipitation assays showed that EED was implicated in TGF-β-induced transcriptional repression of CDH1 and miR-200 family genes through the regulation of histone H3 methylation and EZH2 occupancies on their regulatory regions. Our study demonstrated a novel role of EED, which regulates PRC2 activity and histone methylation during TGF-β-induced EMT of cancer cells.
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
authors.forename: Dulamsuren
authors.initials: D
authors.lastname: Oktyabri
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tange
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Terashima
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ishimura
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan. Electronic address: suzuki-t@staff.kanazawa-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D063151:Polycomb Repressive Complex 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C491488:EED protein, human; D006657:Histones; D018398:Homeodomain Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; D063151:Polycomb Repressive Complex 2
keywords: Cancer progression; Epithelial–mesenchymal transition; Histone methylation; Transcriptional regulation; microRNA