Research Papers:
Direct regulation of E-cadherin by targeted histone methylation of TALE-SET fusion protein in cancer cells
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Abstract
Hyun-Soo Cho1,*, Jeong Gu Kang3,*, Jae-Hye Lee1,4,*, Jeong-Ju Lee2, Seong Kook Jeon3, Jeong-Heon Ko3, Dae-Soo Kim2, Kun-Hyang Park2, Yong-Sam Kim3, Nam-Soon Kim1,2,4
1Genomics Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea
2Human Derived Material Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea
3Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, Republic of Korea
4Department of Functional Genomics, Korea University of Science and Technology, Daejeon, 305-333, Republic of Korea
*These authors have contributed equally to this work
Correspondence to:
Nam-Soon Kim, e-mail: [email protected]
Keywords: TALEN, histone methylation, migration, cancer
Received: February 12, 2015 Accepted: June 09, 2015 Published: June 19, 2015
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.
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