Organization of the human corticosteroid binding globulin geneand analysis of its 5’-flankingregion

Abstract

The structure of the human corticosteroid binding globulin (CBG) gene has been determined, and restriction endonuclease maps of human placentalDNA and cloned genomic DNA indicate that CBG isencoded by a single gene. The transcription unit forhepatic CBG mRNA comprises five exons distributedover approximately 19 kilobases (kb), and nucleaseprotection and primer extension studies using human liver RNA demonstrate that the first exon spans70 base pairs (bp). Typical of many eukaryotic promoters, sequences that resemble TATA and CAAT-box motifs are centered 28 bp and 73 bp upstreamfrom the origin of transcription, respectively. In addition, six highly conserved sequence elements, responsible for efficient, liver-specific expression ofthe mouse albumin gene, are located within the first200 bp of the 5’-flanking region. Further analysis ofa region (500 bp) immediately 5’ of the transcriptionstart site, however, failed to reveal sequences thatmight correspond to known steroid hormone response elements. When compared to other serineprotease inhibitor genes, the organization of thehuman CBG gene is most closely related to thehuman α1-proteinase inhibitor and α1-antichymo-trypsin genes. It would therefore appear that theseproteins are derived from a common ancestral gene, and this supports the concept that they may befunctionally related. © 1989 by The Endocrine Society.