Structure and transcription regulation of the human insulin-like growth factor binding protein 4 gene (IGFBP4)

Insulin-like growth factor binding protein 4 (IGFBP-4) is locally produced by normal human bone cells and acts as a potent inhibitor of IGF action in this tissue. PTH and a cAMP analog increase the expression of IGFBP4 mRNA in human osteoblast cells. We now show that the human IGFBP4 gene is contained within 15.3 kb with the transcription initiation site located 28 bp downstream of a TATA box sequence and 286 bp upstream of the translation initiation codon. The 3'-end of the mRNA was identified at position 14281, but no conserved poly(A) addition signal was found within 30 bp upstream of this site. Deletion mutagenesis located the core promoter activity downstream of position -289, and the transcription activity disappeared at -6. Stimulation with 0.5 mM dibutyryl-cAMP resulted in a twofold increase of promoter activity. Elements responsible for the cAMP response reside between positions -869 and -6.