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dc.contributor.author이영식-
dc.date.accessioned2018-02-05T06:06:27Z-
dc.date.available2018-02-05T06:06:27Z-
dc.date.issued2015-01-
dc.identifier.citationANIMAL CELLS AND SYSTEMS, v. 19, No. 1, Page. 16-29en_US
dc.identifier.issn1976-8354-
dc.identifier.issn2151-2485-
dc.identifier.urihttp://www.tandfonline.com/doi/abs/10.1080/19768354.2014.991351-
dc.identifier.urihttp://hdl.handle.net/20.500.11754/35418-
dc.description.abstractThe transcription factor Kruppel-like factor 4 (KLF4) is highly expressed and plays an important role in maintaining stemness in embryonic stem cells (ES cells). However, how the expression of KLF4 is regulated has not been well documented. To elucidate the molecular mechanisms controlling the expression of human KLF4 (hKLF4) in ES cells, a 3685-bp DNA fragment upstream of the hKLF4 gene was isolated and the 5 '-regulatory region was characterized, from which two regions highly conserved with rodents were identified. In addition, one consensus binding site for members of the TCF family #TBS# was identified within each conserved region. Tcf7l1, a member of the TCF family, is highly expressed in ES cells and has been identified as a crucial regulator of the pluripotency gene regulatory network in ES cells. Therefore, the possible transcriptional mechanisms by which Tcf7l1 regulates hKLF4 expression in ES cells were investigated. In the present study, gel retardation showed that Tcf7l1 preferentially bound to the distal TBS element. In addition, overexpression of Tcf7l1 significantly increased the expression of endogenous KLF4 mRNA in both HEK293 #low nuclear beta-catenin# and HCT116 cells #high nuclear beta-catenin#. In both cell lines, the relative expression of KLF4 mRNA was correlated with the increased Tcf7l1 gene expression, but not with active beta-catenin activities. In transient transfection assays, the hKLF4-3685 construct showed 15-fold activity compared to a deletion construct #hKLF4-1033# in HCT116 cells, while significant activity was not observed in HEK293 cells. As the full promoter construct was active only in HCT116 cells, not HEK293 cells, endogenous Tcf4 may activate promoter with active beta-catenin. However, Tcf7l1 overexpression showed similar promoter activation in both cells. While Tcf7l1 stimulated the hKLF-3685 promoter by 4-6 fold, it did not stimulate the hKLF4-1033 construct at all in either of the cell lines, revealing that the Tcf7l1 responsive element must be present -3685 to -1033 upstream of the translation initiation site, which was consistent with the gel retardation data. Collectively, the present results demonstrated that distal TBS was essential for TCF-mediated transcriptional activation of the hKLF4 promoter. In addition, while TBS responds to Tcf4 in a Wnt/A beta -catenin-dependent manner, it responded to Tcf7l1 independent of active beta-catenin activity.en_US
dc.description.sponsorshipWe thank Dr Jae-Ryong Kim at Yeungnam University for the Tcf7l1 expression plasmid. This research was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education [2013R1A1A2064121 and 2010-0025006], by a grant from the National Research Foundation of Korea grant funded by the Korean Government [No. 2011-0030772 to YS Lee], and a grant from the National R& D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea [1120100].en_US
dc.language.isoen_USen_US
dc.publisherTAYLOR & FRANCIS LTDen_US
dc.subjectTCF-REen_US
dc.subjectTcf7l1en_US
dc.subjectbeta-cateninen_US
dc.subjectKLF4en_US
dc.subjecttranscriptionen_US
dc.subjectCELL SELF-RENEWALen_US
dc.subjectEMBRYONIC STEM-CELLSen_US
dc.subjectBETA-CATENIN BINDINGen_US
dc.subjectCOLORECTAL-CANCERen_US
dc.subjectDEFINED FACTORSen_US
dc.subjectDNA-DAMAGEen_US
dc.subjectTCF3en_US
dc.subjectDIFFERENTIATIONen_US
dc.subjectPLURIPOTENCYen_US
dc.subjectEXPRESSIONen_US
dc.titleTcf7l1-mediated transcriptional regulation of Kruppel-like factor 4 geneen_US
dc.typeArticleen_US
dc.relation.no1-
dc.relation.volume19-
dc.identifier.doi10.1080/19768354.2014.991351-
dc.relation.page16-29-
dc.relation.journalANIMAL CELLS AND SYSTEMS-
dc.contributor.googleauthorPark, MS-
dc.contributor.googleauthorKausar, R-
dc.contributor.googleauthorKim, MW-
dc.contributor.googleauthorCho, SY-
dc.contributor.googleauthorLee, YS-
dc.contributor.googleauthorLee, MA-
dc.relation.code2015011608-
dc.sector.campusE-
dc.sector.daehakCOLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E]-
dc.sector.departmentDEPARTMENT OF MOLECULAR AND LIFE SCIENCE-
dc.identifier.pidyslee-


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