Possible roles of the 3'-flanking sequences of the human activin beta A 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 beta A/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 AP-1 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 beta A subunit gene play an important role in its expression.
Tanimoto
K
K
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan.
Murakami
K
K
Fukamizu
A
A
D028341:Activins; D017500:Adenovirus E1A Proteins / Q000494:pharmacology; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D016384:Consensus Sequence; D004789:Enzyme Activation; D004920:Erythropoiesis / Q000187:drug effects / Q000235:genetics*; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D007265:Inhibins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D011061:Poly A / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012097:Repressor Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D028341:Activins; D011061:Poly A; D007265:Inhibins; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate