Structure of the rat insulin-like growth factor binding protein-4 gene.

A family of six distinct insulin-like growth factor binding proteins (IGFBPs) have been isolated and their cDNA sequences characterized from rat and human species. Recently, the gene structures of the first three IGFBPs (IGFBP-1, -2 and -3) have also been determined. We now report the isolation of the rat IGFBP-4 gene and its genomic organization, as well as the DNA sequence of the promoter region. Rat IGFBP-4 gene spans at least 12 kilobases (kb) of the genomic sequence. It consists of four exons separated by three introns with approximate size of 6.4, 0.6 and 2.7 kb. A single transcriptional start site is located at 249 nucleotides upstream of the translational initiation ATG codon. The rat IGFBP-4 gene possesses a typical TATA box and a CAAT box, as well as multiple potential cis elements, including three cAMP responsive elements, three AP-1 binding sites and one progesterone receptor binding site in the 5' flanking region. The presence of these potential cis elements supports the tissue-specific expression of the IGFBP-4 gene.