title: Transcriptional regulation of OCT4 by the ETS transcription factor ESE-1 in NCCIT human embryonic carcinoma cells.
abstract: 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.
authors: Department of Biomedical Science, College of Life Science, CHA University, Seongnam-Si, Gyeonggi-Do, South Korea.
authors: Sung-Won
authors: SW
authors: Park
authors: Department of Biomedical Science, College of Life Science, CHA University, Seongnam-Si, Gyeonggi-Do, South Korea.
authors: Hyun-Jin
authors: HJ
authors: Do
authors: Department of Biomedical Science, College of Life Science, CHA University, Seongnam-Si, Gyeonggi-Do, South Korea.
authors: Woo Tae
authors: WT
authors: Ha
authors: Department of Biomedical Science, College of Life Science, CHA University, Seongnam-Si, Gyeonggi-Do, South Korea.
authors: Mi-Hee
authors: MH
authors: Han
authors: Department of Biomedical Science, College of Life Science, CHA University, Seongnam-Si, Gyeonggi-Do, South Korea.
authors: Heung-Mo
authors: HM
authors: Yang
authors: Department of Biomedical Science, College of Life Science, CHA University, Seongnam-Si, Gyeonggi-Do, South Korea.
authors: Soo-Hong
authors: SH
authors: Lee
authors: Department of Animal & Food Bioscience, College of Natural Science, Konkuk University, Chungju, Chungbuk, South Korea.
authors: Hyuk
authors: H
authors: Song
authors: Department of Animal Sciences, Chungbuk National University, Cheongju, Chungbuk, South Korea.
authors: Nam-Hyung
authors: NH
authors: Kim
authors: Department of Biomedical Science, College of Life Science, CHA University, Seongnam-Si, Gyeonggi-Do, South Korea. Electronic address: jaehwan_k@cha.ac.kr.
authors: Jae-Hwan
authors: JH
authors: Kim
mesh_terms: D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D009154:Mutation; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; C105529:ELF3 protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors
keywords: ESE-1; NCCIT cells; OCT4 promoter; Transcription