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A Tcf/Lef element within the enhancer region of the human NANOG gene plays a role in promoter activation

Title
A Tcf/Lef element within the enhancer region of the human NANOG gene plays a role in promoter activation
Author
정일엽
Keywords
NANOG; Dvl-1; Tcf/Lef; beta-Catenin; GSK-3 beta
Issue Date
2011-07
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE, 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
Citation
Biochemical and biophysical research communications,Vol.410 No.3 [2011],637-642
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.
URI
http://www.sciencedirect.com/science/article/pii/S0006291X11010023?_rdoc=1&_fmt=high&_origin=gateway&_docanchor=&md5=b8429449ccfc9c30159a5f9aeaa92ffbhttp://hdl.handle.net/20.500.11754/36627
ISSN
0006-291X
DOI
10.1016/j.bbrc.2011.06.044
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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