MULTIPLE AND ESSENTIAL SP1 BINDING-SITES IN THE PROMOTER FOR TRANSFORMING GROWTH-FACTOR-BETA TYPE-I RECEPTOR

Maximal gene expression driven by the promoter for the transforming gr owth factor beta type I receptor (TGF-beta RI) occurs with a 1.0-kilob ase pair fragment immediately upstream of exon 1, This region lacks a typical TATA box but contains CCAAT boxes, multiple Spl, and PEBP2/CBF alpha binding sites among other possible cis-acting elements, Alterat ions within two CCAAT box sequences do not mitigate reporter gene expr ession driven by the basal promoter, and no nuclear factor binds to ol igonucleotides encompassing these sites, In contrast, other deletions or site-specific mutations reveal an essential Sal site in the basal p romoter and several dispersed upstream Spl sites that contribute to ma ximal reporter gene expression, The proportions of transcription facto rs Sp1 and Sp3, and their ratios of binding to consensus Elements, are maintained in bone cells at different stages of differentiation, Fina lly, nuclear factor that binds to PEBP2/CBF alpha-related cis-acting e lements in the basal promoter sequence also occurs in osteoblasts. Our studies reveal that constitutive expression of TGF-beta RI may be det ermined by constitutive nuclear factor binding to Spl sites, whereas o ther elements may account for the variations in TGF-beta RI levels tha t parallel. changes in bane cell differentiation or activity.