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 prod uced 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 o f IGFBP4 mRNA in human osteoblast cells. We now show that the human IG FBP4 gene is contained within 15.3 kb with the transcription initiatio n site located 28 bp downstream of a TATA box sequence and 286 bp upst ream of the translation initiation codon. The 3'-end of the mRNA was i dentified at position 14281, but no conserved poly(A) addition signal was found within 30 bp upstream of this site. Deletion mutagenesis loc ated the core promoter activity downstream of position -289, and the t ranscription activity disappeared at -6. Stimulation with 0.5 mM dibut yryl-cAMP resulted in a twofold increase of promoter activity. Element s responsible for the cAMP response reside between positions -869 and -6. (C) 1998 Academic Press.