Genomic Organization, 5’-Upstream Sequence, and Chromosomal Localization of an Insulinoma-associated Intronless GenIeA, -1

IA-1 is a novelc DNA originally isolated froma human insulinoma subtraction library (ISL-153). It encodes a protein containing both a zinc finger DNA-binding domain and a putative prohormone domain. IA-1 transcripts have been found thus far only in tumors of neuroendocrine origin. Clinical studies have shown that IA-1 is a sensitive marker for neuroendocrine differentiation of human lung tumors. In this study, we cloned and sequenced the enItiAr-e1 gene and its 5‘-upstream region from a human liver genomic library. In situ hybridization localized theIA -1 gene to the short arm of human chromosome 20. Sequence analysis and restriction enzyme mapping showed that thIeA -1 gene is uninterrupted and appears to be intronless. Evidence thIAat- 1 is an intronless gene that can translate into protein was obtained from in vitro translation studies that showed that both IA-1 cDNA and IA-1 genomic DNA yielded identical protein products of approximately 61,000 daltons. Examination of the 5' upstream regio(n2 090 base pairs) revealed several tissue-specific regulatory elements, including glucokinase upstream promoter elements aan d P it-1 factor binding site. The presence of several different upstream regulatory elements may account for IA-1 gene expression in different neuroendocrine tumors.