Promoter sequences of the human transforming growth factor-β1 gene responsive to transforming growth factor-β1 autoinduction

Two distinct regions of the transforming growth factor (TGF)-β1 promoter are responsive to autoregulation. Sequences located between nucleotides -454 to -323 and between the two major transcriptional start sites have positive regulatory activities and are induced by TGF-β1 in A-549 cells. The chloramphenicol acetyltransferase activity of the upstream human TGF-β1 promoter-chloramphenicol acetyltransferase gene is increased 8- to 10-fold by treatment of cells with TGF-β1, whereas that of the second promoter is increased approximately 3- to 4-fold. Using an S1 nuclease protection assay of chloramphenicol acetyltransferase mRNA, we found that the steady-state expression of chloramphenicol acetyltransferase mRNA also is markedly increased. Seven distinct factors present in nuclear extracts from A-549 cells interact with the sequences between -454 and -323, strongly supporting the involvement of sequence-specific transcription factors in the transcriptional autoactivation of the human TGF-β1 gene.