Regulation of the transforming growth factor-beta 1 and -beta 3 promoters by transcription factor Sp1

Gene. 1993 Jul 30;129(2):223-8. doi: 10.1016/0378-1119(93)90272-5.


The promoter regions of the genes encoding the three mammalian transforming growth factors-beta (TGF-beta 1, -beta 2, and -beta 3) show little similarity in sequence, suggesting diverse transcriptional control. As a step towards understanding transcriptional regulation of the individual TGF-beta genes we tested each of the three TGF-beta promoter regions (pTGF-beta) for stimulation by the transcription factor Sp1, given that several possible Sp1-binding sites were identified by sequence analysis in pTGF-beta 1 and pTGF-beta 3. A Drosophila melanogaster cell culture system was employed to examine expression levels of pTGF-beta::cat constructs coexpressed with an Sp1 expression plasmid in a cell background devoid of any Sp1 homolog. While both pTGF-beta 1 and pTGF-beta 3 were strongly stimulated by Sp1, pTGF-beta 2 was completely unaffected. Promoter fragments of the TGF-beta 1 and TGF-beta 3 genes, but not TGF-beta 2 were able to compete for binding of Sp1 to DNA oligomers containing consensus Sp1-binding sites. Moreover, specific binding to pTGF-beta 1 and pTGF-beta 3 fragments was seen using pure Sp1 or nuclear protein extracts. Thus, TGF-beta 1 and TGF-beta 3 (but not TGF-beta 2) are regulated by the transcription factor Sp1, indicating differential transcriptional regulation of genes whose protein products are functionally very similar.

MeSH terms

  • Acetylation
  • Animals
  • Base Sequence
  • Binding, Competitive
  • Cells, Cultured
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Consensus Sequence
  • Drosophila melanogaster
  • Humans
  • Mammals
  • Molecular Sequence Data
  • Promoter Regions, Genetic* / drug effects
  • Promoter Regions, Genetic* / physiology
  • Recombinant Fusion Proteins
  • Sp1 Transcription Factor / physiology*
  • Transcriptional Activation*
  • Transfection
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics*


  • Recombinant Fusion Proteins
  • Sp1 Transcription Factor
  • Transforming Growth Factor beta
  • Chloramphenicol O-Acetyltransferase