Structural characterization of a brain-specific promoter region directing transcription of the rat prepro-gastrin-releasing peptide gene.

Expression of the mammalian prepro-gastrin-releasing peptide (preproGRP) gene has been shown to be restricted to neural and neuroendocrine cell types. In this paper, the structure and nucleotide sequence of the rat preproGRP gene coding regions and promoter is described and analyzed. The gene is divided into 3 exons, encoding a signal sequence, the 29 amino acid rat GRP, and a 92 amino acid extension peptide. While the overall prohormone structure is similar to that predicted from the sequence of the human gene, differences in transcription are apparent. Several forms of the rat preproGRP mRNA are found in brain: a 1.1 kb form which initiates in both brain and gut primarily from a TATAA-directed promoter, and less abundant forms of about 1.5 kb, whose initiation sites are heterogeneous, located 300-400 base pairs upstream of the 1.1 kb initiation site, and found only in spinal cord and a subset of brain nuclei expressing preproGRP mRNA. Comparison of the human and rat promoter region sequences identifies regions of high similarity upstream from both the 1.1 kb and 1.5 kb mRNA initiation sites, which may be important in the cell type-specific regulation of the preproGRP gene.