A Tcf/Lef element within the enhancer region of the human NANOG gene plays a role in promoter activation
- Authors
- Kim, Chang Gun; Chung, Il-Yup; Lim, Yoongho; Lee, Young Han; Shin, Soon Young
- Issue Date
- Jul-2011
- Publisher
- Academic Press
- Keywords
- NANOG; Dvl-1; Tcf/Lef; beta-Catenin; GSK-3 beta
- Citation
- Biochemical and Biophysical Research Communications, v.410, no.3, pp.637 - 642
- Indexed
- SCIE
SCOPUS
- Journal Title
- Biochemical and Biophysical Research Communications
- Volume
- 410
- Number
- 3
- Start Page
- 637
- End Page
- 642
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/37293
- DOI
- 10.1016/j.bbrc.2011.06.044
- ISSN
- 0006-291X
- Abstract
- NANOG is a homeodomain-containing transcription factor that is essential for the maintenance of pluripotency and self-renewal in embryonic stem cells. However, the molecular mechanisms underlying the regulation of NANOG expression in human cells remain largely unknown. Here, we investigated the role of Tcf/Lef response elements located in the enhancer of the human NANOG gene. We found that forced expression of Lef1 or beta-catenin stimulated human NANOG promoter activity, while shRNA-mediated knockdown of beta-catenin reduced Lef1-induced NANOG promoter activation. Deletion or mutation of the Tcf/Lef element within the enhancer region of the human NANOG gene completely abrogated Lef1-induced NANOG promoter activity. The results of a chromatin immunoprecipitation assay demonstrated that Lefl and beta-catenin bind to the Tcf/Lef element in the enhancer region of the NANOG gene. Forced expression of GSK-31 inhibited basal, Lefl -induced, and beta-catenin-induced NANOG promoter activity, while treatment with the GSK-3 beta inhibitor SB216763 resulted in the accumulation of beta-catenin and NANOG protein. Furthermore, DvI-1-induced NANOG promoter activity was abrogated by the expression of beta-catenin shRNA. Stable overexpression of Dvl-1 caused beta-catenin and NANOG to accumulate. These results indicate that the Tcf/Lef response element in the enhancer region of the human NANOG gene is able to stimulate NANOG gene transcription. (C) 2011 Elsevier Inc. All rights reserved.
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