title: Regulation of OCT4 gene expression by liver receptor homolog-1 in human embryonic carcinoma cells.
abstract: We demonstrate the regulation of OCT4 gene expression mediated by liver receptor homolog-1 (LRH-1) in human embryonic carcinoma cells. LRH-1 and OCT4 are co-expressed in undifferentiated NCCIT cells and decreased during retinoic acid-induced differentiation. Dose-dependent overexpression of LRH-1 transactivated the OCT4 promoter activity and its dominant negative form with a deletion of activation function-2 motif reduced the activity even in the presence of LRH-1. The OCT4 promoter contains potent three LRH-1 binding sites; one within conserved region (CR) 1 and two within CR2. Mutagenesis of each binding site affected the decrease in OCT4 promoter activity and the 2nd binding site mutant most significantly reduced the transcriptional activity, compared to that of 1st and 3rd binding site mutants, respectively. Simultaneous disruption of 2nd and 3rd binding sites led to significant down-regulation of the activity even in the presence of 1st binding site-containing CR1. Moreover, mutation of each binding element within native or exogenous minimal promoter-driven CR1 or CR2 also decreased the promoter activity to some different extent, suggesting that three binding elements may be implicated in the induction of the full-activity of OCT4 promoter. In vivo binding assay revealed the 2nd and 3rd binding motifs within CR2 were more enriched than the 1st one within CR1. Taken together, our study indicates that LRH-1 acts as a transcriptional activator in the regulation of OCT4 gene expression through the cooperative interaction with three binding sites directly or/and indirectly.
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-Do, South Korea.
authors.forename: BoReum
authors.initials: B
authors.lastname: Sung
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Do
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Park
authors.forename: Sun-Hyung
authors.initials: SH
authors.lastname: Huh
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Oh
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Chung
authors.forename: Man-Jong
authors.initials: MJ
authors.lastname: Kang
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
authors.forename: Nam-Hyung
authors.initials: NH
authors.lastname: Kim
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Kim
mesh_terms: D001665:Binding Sites; D018236:Carcinoma, Embryonal / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050814:Octamer Transcription Factor-3 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology
chemical_list: C082631:NR5A2 protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D014212:Tretinoin