Regulation of the transforming growth factor-β1 and -β3 promoters by transcription factor Spl

Abstract

The promoter regions of the genes encoding the three mammalian transforming growth factors-β (TGF-β1, -β2, and -β3) show little similarity in sequence, suggesting diverse transcriptional control. As a step towards understanding transcriptional regulation of the individual TGF-β genes we tested each of the three TGF-β promoter regions ( pTGFβ) for stimulation by the transcription factor Spl, given that several possible Spl-binding sites were identified by sequence analysis in pTGF-β1 and pTGF-β3. A Drosophila melanogaster cell culture system was employed to examine expression levels of pTGF-β::cat constructs coexpressed with an Spl expression plasmid in a cell background devoid of any Spl homolog. While both pTGF-β1 and pTGF-β3 were strongly stimulated by Spl, pTGF-β2 was completely unaffected. Promoter fragments of the TGF-β1 and TGF-β3 genes, but not TGF-β2 were able to compete for binding of Spl to DNA oligomers containing consensus Spl-binding sites. Moreover, specific binding to pTGF-β1 and pTGF-β3 fragments was seen using pure Spl or nuclear protein extracts. Thus, TGF-β1 and TGF-β3 (but not TGF-β2) are regulated by the transcription factor Spl, indicating differential transcriptional regulation of genes whose protein products are functionally very similar.