Oct-4 regulates alternative platelet-derived growth factor alpha receptor gene promoter in human embryonal carcinoma cells

Expression of the platelet-derived growth factor alpha-receptor (PDGF alpha R) gene is tightly controlled in mammalian embryogenesis. A well established model system to study human embryogenesis is the embryonal carcinoma cell line Tera2, We have shown previously that retinoic acid-differentiated Tera2 cells express two PDGF alpha R transcripts of 6.4 kilobase pairs (kb) (encoding the full-length receptor) and 3.0 kb, respectively, whereas in contrast, undifferentiated Tera2 cells express PDFG alpha R transcripts of 1.5 kb and 5.0 kb, Here we show that this switch in PDGF alpha R expression pattern during differentiation of Tera2 cells results from alternative promoter use, In undifferentiated cells, a second promoter is used, which is located in intron 12 of the PDGF alpha R gene, Functional analysis shows that this promoter contains a consensus octamer motif, which can be bound by the POU domain transcription factor Oct-4, Oct-4 is expressed in undifferentiated Tera2 cells but not in retinoic acid-induced differentiated cells, Mutation of the octamer motif decreases promoter activity, while ectopic expression of Oct-4 in differentiated Tera2 cells specifically enhances the activity of this PDGF alpha R promoter, Therefore, we suggest that an important aspect in the maintenance of the undifferentiated state of human embryonal carcinoma cells results from Oct-4 expression, which thereupon activates this PDGF alpha R promoter.