REGULATION OF THE TRANSFORMING GROWTH-FACTOR-BETA-1 AND FACTOR-BETA-3 PROMOTERS BY TRANSCRIPTION FACTOR SP1

The promoter regions of the genes encoding the three mammalian transforming growth factors-beta (TGF-beta1, -beta2, and -beta3) 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 Spl-binding sites were identified by sequence analysis in pTGF-beta1 and pTGF-beta3. 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-beta1 and pTGF-beta3 were strongly stimulated by Sp1, pTGF-beta2 was completely unaffected. Promoter fragments of the TGF-beta1 and TGF-beta3 genes, but not TGF-beta2 were able to compete for binding of Sp1 to DNA oligomers containing consensus Sp1-binding sites. Moreover, specific binding to pTGF-beta1 and pTGF-beta3 fragments was seen using pure Sp1 or nuclear protein extracts. Thus, TGF-beta1 and TGF-beta3 (but not TGF-beta2) are regulated by the transcription factor Sp1, indicating differential transcriptional regulation of genes whose protein products are functionally very similar.