Characterization of cis-acting elements and transacting factors involved in the tissue-specific and developmental regulation of IGFBP-1 gene expression.

The liver-specificity of insulin-like growth factor binding protein-1 (IGFBP-1) gene promoter activity has been studied by transient transfection in rat hepatoma cell lines, rat fibroblasts and human cervical carcinoma cells, and shown to be dependent on HNF1. Regulation of IGFBP-1 gene expression has also been studied in rat liver by Northern blot and run-on assays during development, specifically during the perinatal period. The results suggest (1) that the increases in mRNA at birth and +1 day post-natally result from increased transcription and (2) that no decrease in transcription activity accompanies the rapid IGFBP-1 mRNA decay during the neonatal period, arguing for post-transcriptional regulation. Support for transcriptional regulation during the neonatal period was obtained from in vitro footprinting experiments and gel shift data. Three trans-acting factors interact with the h-IGFBP-1 promoter between nt -265 and -305. Two of these, Pc and PHS, were expressed throughout development, as well as during adulthood, and interacted with cis-elements spanning nt -295 to -305 and -265 to -285, respectively. The third, Pa, was expressed only when IGFBP-1 gene expression was high, and interacted with cis-elements spanning nt -285 to -295.