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

The promoter regions of the genes encoding the three mammalian transfo rming 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 indivi dual TGF-beta genes we tested each of the three TGF-beta promoter regi ons (pTGF-beta) for stimulation by the transcription factor Sp1, given that several possible Spl-binding sites were identified by sequence a nalysis in pTGF-beta1 and pTGF-beta3. A Drosophila melanogaster cell c ulture system was employed to examine expression levels of pTGF-beta:: cat constructs coexpressed with an Sp1 expression plasmid in a cell ba ckground devoid of any Sp1 homolog. While both pTGF-beta1 and pTGF-bet a3 were strongly stimulated by Sp1, pTGF-beta2 was completely unaffect ed. Promoter fragments of the TGF-beta1 and TGF-beta3 genes, but not T GF-beta2 were able to compete for binding of Sp1 to DNA oligomers cont aining consensus Sp1-binding sites. Moreover, specific binding to pTGF -beta1 and pTGF-beta3 fragments was seen using pure Sp1 or nuclear pro tein extracts. Thus, TGF-beta1 and TGF-beta3 (but not TGF-beta2) are r egulated by the transcription factor Sp1, indicating differential tran scriptional regulation of genes whose protein products are functionall y very similar.