title: Direct regulation of E-cadherin by targeted histone methylation of TALE-SET fusion protein in cancer cells.
abstract: TALE-nuclease chimeras (TALENs) can bind to and cleave specific genomic loci and, are used to engineer gene knockouts and additions. Recently, instead of using the FokI domain, epigenetically active domains, such as TET1 and LSD1, have been combined with TAL effector domains to regulate targeted gene expression via DNA and histone demethylation. However, studies of histone methylation in the TALE system have not been performed. Therefore, in this study, we established a novel targeted regulation system with a TAL effector domain and a histone methylation domain. To construct a TALE-methylation fusion protein, we combined a TAL effector domain containing an E-Box region to act as a Snail binding site and the SET domain of EHMT 2 to allow for histone methylation. The constructed TALE-SET module (TSET) repressed the expression of E-cadherin via by increasing H3K9 dimethylation. Moreover, the cells that overexpressed TSET showed increased cell migration and invasion. This is the first phenotype-based study of targeted histone methylation by the TALE module, and this new system can be applied in new cancer therapies to reduce side effects.
authors.affiliation: Genomics Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea.
authors.forename: Jeong Gu
authors.initials: JG
authors.lastname: Kang
authors.affiliation: Genomics Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea.|Department of Functional Genomics, Korea University of Science and Technology, Daejeon, 305-333, Republic of Korea.
authors.forename: Jae-Hye
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Human Derived Material Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea.
authors.forename: Jeong-Ju
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea.
authors.forename: Seong Kook
authors.initials: SK
authors.lastname: Jeon
authors.affiliation: Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea.
authors.forename: Jeong-Heon
authors.initials: JH
authors.lastname: Ko
authors.affiliation: Human Derived Material Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea.
authors.forename: Dae-Soo
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Human Derived Material Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea.
authors.forename: Kun-Hyang
authors.initials: KH
authors.lastname: Park
authors.affiliation: Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea.
authors.forename: Yong-Sam
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Genomics Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea.|Human Derived Material Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea.|Department of Functional Genomics, Korea University of Science and Technology, Daejeon, 305-333, Republic of Korea.
authors.forename: Nam-Soon
authors.initials: NS
authors.lastname: Kim
mesh_terms: D001665:Binding Sites / Q000235:genetics; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D045325:HCT116 Cells; D006367:HeLa Cells; D056488:Histone Chaperones / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014945:Wound Healing
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D006657:Histones; D018398:Homeodomain Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C513473:SET protein, human; C097504:TGIF1 protein, human; D014157:Transcription Factors
keywords: TALEN; cancer; histone methylation; migration