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Title 

Direct regulation of E-cadherin by targeted histone methylation of TALE-SET fusion protein in cancer cells

 

TALE-SET 재조합 단백질의 targeted histone methylation에 의한 E-Cadherin의 발현 조절

Authors 

Hyun Soo ChoJeong Gu KangJae Hye LeeJeong Ju LeeSeong Kook JeonJeong Heon KoDae Soo KimKun Hyang ParkYong Sam KimNam-Soon Kim

Publisher 

Impact Journals

Issue Date 

2015

Citation 

Oncotarget, vol. 6, no. 27, pp. 23837-23844

Keywords 

CancerHistone methylationMigrationTALEN

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.

ISSN 

1949-2553

Link 

http://dx.doi.org/10.18632/oncotarget.4340

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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