Possible Roles of the 3′-Flanking Sequences of the Human Activin βA-Subunit Gene in Its Expression

Tumor promoter 12-O-tetradecanoylphorbol-13 -acetate stimulates an increase in erythroid differentiation activity in human fibrosarcoma HT1080 cells. Here, we demonstrate that this process involves a rapid accumulation of five species of activin βA/erythroid differentiation factor mRNA, followed by protein kinase C activation, and that variation in size of the activin transcripts is due to multiple 3′ ends, presumably reflecting an alternative polyadenylation. In transiently transfected HT1080 cells, a 97-bp DNA fragment containing an API consensus sequence (TGAGTCA) located in the 3′-flanking region of the activin gene was capable of activating the heterologous herpes simplex virus thymidine kinase (tk) and SV40 early promoters, and a cotransfected c-Jun enhanced these fusion promoter activities. The deletion of TGAG sequences from the AP-1 element in the 97-bp DNA sequence context abolished its c-Jun-mediated activation from the tk promoter even in HT1080 cells overexpressing stably transfected c-Jun. Cotransfected adenovirus E1A products repressed the tk promoter activity enhanced by the activin AP-1 element itself or in concert with transiently transfected c-Jun, indicating that the putative AP-1 sequence acts as an activator element, depending upon c-Jun activity. These results suggest that the 3′-flanking DNA sequences of the human activin βA subunit gene play an important role in its expression.