Promoter sequences of the human transforming growth factor-beta 1 gene responsive to transforming growth factor-beta 1 autoinduction.
Two distinct regions of the transforming growth factor (TGF)-beta 1 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-beta 1 in A-549 cells. The chloramphenicol acetyltransferase activity of the upstream human TGF-beta 1 promoter-chloramphenicol acetyltransferase gene is increased 8- to 10-fold by treatment of cells with TGF-beta 1, whereas that of the second promoter is increased approximately 3- to 4-fold. Using an S1 nuclease protection assay of chloramphenicol acetyl-transferase 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-beta 1 gene.
Kim
S J
SJ
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892.
Jeang
K T
KT
Glick
A B
AB
Sporn
M B
MB
Roberts
A B
AB
D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D015291:Transforming Growth Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D006133:Growth Substances; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D015291:Transforming Growth Factors