Genomic organization, 5'-upstream sequence, and chromosomal localization of an insulinoma-associated intronless gene, IA-1.
IA-1 is a novel cDNA originally isolated from a 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 entire IA-1 gene and its 5'-upstream region from a human liver genomic library. In situ hybridization localized the IA-1 gene to the short arm of human chromosome 20. Sequence analysis and restriction enzyme mapping showed that the IA-1 gene is uninterrupted and appears to be intronless. Evidence that IA-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 region (2090 base pairs) revealed several tissue-specific regulatory elements, including glucokinase upstream promoter elements and a Pit-1 factor binding site. The presence of several different upstream regulatory elements may account for IA-1 gene expression in different neuroendocrine tumors.
Lan
M S
MS
Laboratory of Oral Medicine, NIDR, National Institutes of Health, Bethesda, Maryland 20892.
Li
Q
Q
Lu
J
J
Modi
W S
WS
Notkins
A L
AL
D001483:Base Sequence; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007340:Insulinoma / Q000235:genetics*; D007438:Introns; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D012097:Repressor Proteins; D015183:Restriction Mapping; D016335:Zinc Fingers / Q000235:genetics*
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C087342:INSM1 protein, human