Implication of human OCT4 transactivation domains for self-regulatory transcription.
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.
Lim
Hye-Young
HY
Department of Biomedical Science, CHA Stem Cell Institute, College of Life Science, CHA University, Pochon-si, Gyeonggi-do, South Korea.
Do
Hyun-Jin
HJ
Lee
Won-Young
WY
Kim
Dong-Ku
DK
Seo
Han Geuk
HG
Chung
Hak-Jae
HJ
Park
Jin-Ki
JK
Chang
Won-Kyong
WK
Kim
Jin-Hoi
JH
Kim
Jae-Hwan
JH
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
D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human