STUDIES ON THE STRUCTURE AND REGULATION OF THE RAT SOMATOSTATIN GENE (HORMONE, Z-DNA)

A rat genomic clone encoding the polypeptide hormone somatostatin was characterized and shown to be a single-copy gene, spanning 1.2 kb, and divided into two exons. The sequences of the rat and the human somatostatin genes were compared and found to be highly homologous in the exons but much less homologous in the intron. Upstream from the transcription initiation site the two genes show a significant degree of sequence homology; the pattern of homology is augmented by the homologous distribution of seven alternating purine-pyrimidine sequences in each gene in this region. The genomic clone was shown to contain several sequences which are present at moderate to high copy number in the genome and a sequence which is present at significant levels in both brain and liver poly(A) RNA. Two of these repeated sequences were mapped to 0.75 kb 5\u27 and 2 kb 3\u27 to the gene and shown to be long alternating purine-pyrimidine elements of the moderately repetitive sequence (GT)n. These elements were analyzed by two-dimensional electrophoresis and by fine mapping of S1 nuclease sensitivity and shown to form Z-DNA in plasmids. Short repeating units adjacent to the (GT)n sequences were shown to affect the formation and structure of Z-DNA. The isolation of the gene has enabled the isolation of its promoter sequences, which are being utilized to investigate the regulation of the transcription of the somatostatin gene as the next logical step in furthering the understanding of the biology of somatostatin