Regulation of the transforming growth factor-beta 1 and -beta 3 promoters by transcription factor Sp1.
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.
Geiser
A G
AG
Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Busam
K J
KJ
Kim
S J
SJ
Lafyatis
R
R
O'Reilly
M A
MA
Webbink
R
R
Roberts
A B
AB
Sporn
M B
MB
D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D016384:Consensus Sequence; D004331:Drosophila melanogaster; D006801:Humans; D008322:Mammals; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D011993:Recombinant Fusion Proteins; D016329:Sp1 Transcription Factor / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*
D011993:Recombinant Fusion Proteins; D016329:Sp1 Transcription Factor; D016212:Transforming Growth Factor beta; D015500:Chloramphenicol O-Acetyltransferase