Repression of transforming growth factor beta 1 promoter by the adenovirus oncogene E1A. Identification of a unique GC-rich sequence as a target for E1A repression.
The transforming growth factor beta 1 (TGF-beta 1) is a key regulator of proliferation and differentiation in a wide variety of cell types. It is a potent growth inhibitor for most epithelial, endothelial, lymphoid, and myeloid cells. In the present study, we showed that a DNA virus oncoprotein, E1A, strongly repressed the activity of the TGF-beta 1 promoter in a variety of cell lines. Interestingly, this repression was specific for 12 S E1A because 13 S E1A was much less active in this assay. Analysis of a series of E1A mutants showed that the repression was dependent on the amino terminus and the conserved region 1 of the E1A protein. To identify the target sequence for E1A repression in the TGF-beta 1 promoter, a series of mutant promoters were analyzed and a 10-base pair GC-rich sequence between -91 and -82 was found to be the major target for E1A repression of the promoter. Using chimeric reporter constructs, we provide evidence that the 10-base pair GC-rich sequence is sufficient to impart sequence-specific E1A repression to a heterologous promoter. Additionally, we suggest that the mechanism of E1A repression through this GC-rich element does not involve abrogation of the retinoblastoma control of the TGF-beta 1 promoter.
Datta
P K
PK
Center for Molecular Biology of Oral Diseases, College of Dentistry (M/C 860), University of Illinois, Chicago 60612.
Bagchi
S
S
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D017502:Adenovirus E2 Proteins / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008907:Mink; D008969:Molecular Sequence Data; D009857:Oncogenes / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013045:Species Specificity; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*
D017500:Adenovirus E1A Proteins; D017502:Adenovirus E2 Proteins; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D015500:Chloramphenicol O-Acetyltransferase