Organization of the Human Corticosteroid Binding Globulin Gene and Analysis of Its 5′-Flanking Region

The structure of the human corticosteroid binding globulin (CBG) gene has been determined, and restriction endonuclease maps of human placental DNA and cloned genomic DNA indicate that CBG is encoded by a single gene. The transcription unit for hepatic CBG mRNA comprises five exons distributed over approximately 19 kilobases (kb), and nuclease protection and primer extension studies using human liver RNA demonstrate that the first exon spans 70 base pairs (bp). Typical of many eukaryotic promoters, sequences that resemble TATA and CAAT-box motifs are centered 28 bp and 73 bp upstream from the origin of transcription, respectively. In addition, six highly conserved sequence elements, responsible for efficient, liver-specific expression of the mouse albumin gene, are located within the first 200 bp of the 5'-flanking region. Further analysis of a region (500 bp) immediately 5' of the transcription start site, however, failed to reveal sequences that might correspond to known steroid hormone response elements. When compared to other serine protease inhibitor genes, the organization of the human CBG gene is most closely related to the human alpha 1-proteinase inhibitor and alpha 1-antichymotrypsin genes. It would therefore appear that these proteins are derived from a common ancestral gene, and this supports the concept that they may be functionally related.