Dexamethasone stimulation of rat insulin-like growth factor binding protein-1 (IGFBP-1) promoter activity involves the interaction of multiple transcription factors

Using an improved procedure for transient transfection of H4-II-E rat hepatoma cells, we characterized the cis elements in the proximal promoter of the rat insulin-like growth factor binding protein-1 (rat IGFBP-1) gene that are required for basal (unstimulated) and dexamethasone-stimulated promoter activity. Three sites are required for optimal basal promoter activity: an AP-2 site (nt -286 to -293), the M4 region of the insulin response element (nt -108 to -99), and a hepatocyte nuclear factor-1 (HNF-1) site (nt -62 to -50). In addition to the glucocorticoid response element (nt -91 to -77), participation of two of three accessory sites is required for optimal stimulation by dexamethasone: the M4 and HNF-1 sites, and a third site located between nt -252 and -236. Further study will focus on how the interactions of tissue-specific and hormonally-responsive transcription factors are integrated.