title: Implication of human OCT4 transactivation domains for self-regulatory transcription.
abstract: OCT4 plays a crucial role in pluripotency and self-renewal of embryonic stem cells. OCT4 is also expressed in testicular germ cell tumors (GCTs), suggesting the important function of OCT4 as an oncogenic factor in GCTs. To understand the molecular mechanism of human OCT4 (hOCT4) in tumorigenesis as well as stemness, we identified hOCT4 transactivation domains in human embryonic carcinoma cells. Context analyses of heterologous GAL4 and natural hOCT4 revealed that each N-terminal domain or C-terminal domain independently stimulated transcriptional activity, and that both domains are required for synergistic transactivation by deletion mapping analysis. Dose-dependent overexpression of exogenous hOCT4 significantly decreased the transcriptional activity of the hOCT4 promoter. This inhibition was reversed by the removal of one or both domains. These results suggest that the inhibitory effect of hOCT4 is mediated by transactivation domains, and that the self-regulation of hOCT4 may be mediated via a negative feedback loop in pluripotent cells.
authors.affiliation: Department of Biomedical Science, CHA Stem Cell Institute, College of Life Science, CHA University, Pochon-si, Gyeonggi-do, South Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Lim
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Do
authors.forename: Won-Young
authors.initials: WY
authors.lastname: Lee
authors.forename: Dong-Ku
authors.initials: DK
authors.lastname: Kim
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Chung
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Park
authors.forename: Won-Kyong
authors.initials: WK
authors.lastname: Chang
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Kim
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human