Transcriptional regulation of OCT4 by the ETS transcription factor ESE-1 in NCCIT human embryonic carcinoma cells.
The epithelium-specific ETS transcription factor-1 (ESE-1) is physiologically important in the pathogenesis of various diseases. Recently, OCT4, a transcription factor involved in stem cell pluripotency, has been implicated in tumorigenesis. In this study, we invested the molecular mechanism by which ESE-1 regulates transcription of OCT4 in NCCIT human embryonic carcinoma cells. Real-time PCR analysis revealed that OCT4 levels were high in undifferentiated NCCIT cells but significantly decreased upon retinoic acid-mediated differentiation, concomitant with up-regulation of ESE-1 expression. OCT4 mRNA level rose following shRNA-mediated knockdown of ESE-1, but declined when ESE-1 was overexpressed, suggesting that the expression levels of OCT4 and ESE-1 may be coordinated in an opposite manner. Promoter-reporter assays revealed that induced OCT4 promoter activity in NCCIT cells was significantly down-regulated by ESE-1 overexpression in a dose-dependent manner. The inhibitory effect of ESE-1 on OCT4 promoter activity was relieved by co-expression of an ESE-1 mutant lacking the transactivation domain, but not by mutants lacking other domains. Serial deletion and site-directed mutagenesis of the OCT4 promoter revealed that a potential ETS binding site (EBS) is present in the conserved region 2 (CR2). ESE-1 interacted with the EBS element in CR2 and enrichment of CR2 significantly increased upon RA-mediated differentiation of NCCIT cells, suggesting that this binding is likely to be involved in ESE-1-mediated repression of OCT4 promoter activity upon differentiation. Taken together, the results of this study reveal the molecular details of the mechanism by which the oncogenic factor ESE-1 regulates expression of the stem cell transcription factor OCT4 in pluripotent NCCIT cells.
['Park|Sung-Won|SW|', 'Do|Hyun-Jin|HJ|', 'Ha|Woo Tae|WT|', 'Han|Mi-Hee|MH|', 'Yang|Heung-Mo|HM|', 'Lee|Soo-Hong|SH|', 'Song|Hyuk|H|', 'Kim|Nam-Hyung|NH|', 'Kim|Jae-Hwan|JH|']
D002454:Cell Differentiation D004268:DNA-Binding Proteins D054278:Embryonal Carcinoma Stem Cells D055785:Gene Knockdown Techniques D006801:Humans D009154:Mutation D050814:Octamer Transcription Factor-3 D039904:Pluripotent Stem Cells D011401:Promoter Regions, Genetic D050783:Proto-Oncogene Proteins c-ets D014157:Transcription Factors D014158:Transcription, Genetic D015533:Transcriptional Activation
Transcription ESE-1 NCCIT cells OCT4 promoter