Characterization of the LIM/homeodomain gene islet-1 and single nucleotide screening in NIDDM.
Islet-1 (Isl-1) is a unique transcription factor that binds to the enhancer region of the insulin gene. To evaluate this gene in non-insulin-dependent diabetes mellitus (NIDDM), a full-length human Isl-1 cDNA was isolated and the genomic structure was characterized. The cDNA [2,395 bp plus additional poly(A) residues] contained an open reading frame from an initiator methionine at nucleotide 240 to an opal stop codon at nucleotide 1,286 (GenBank accession number UO7559), encoding a predicted protein of 349 amino acids (39 kDa). From their ends, 23 additional clones were sequenced, revealing 15 incomplete cDNAs and 8 intron-containing partially processed precursors. As determined by Northern blotting and reverse transcriptase-polymerase chain reaction analysis, Isl-1 was most abundantly expressed as a 2.4-kb mRNA in human islets, with a restricted pattern of expression in other adult human tissues. Analysis of genomic clones revealed that Isl-1 is encoded by six exons, varying in size from 168 bp (exon 5) to 1,230 bp (exon 6). Exons 2 and 3 each encode a LIM domain, while the homeodomain is completely contained within exon 4.(ABSTRACT TRUNCATED AT 250 WORDS)
Riggs
A C
AC
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Tanizawa
Y
Y
Aoki
M
M
Wasson
J
J
Ferrer
J
J
Rabin
D U
DU
Vaxillaire
M
M
Froguel
P
P
Permutt
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005796:Genes; D005801:Genes, Homeobox / Q000235:genetics*; D018398:Homeodomain Proteins; D006801:Humans; D007438:Introns / Q000235:genetics; D060850:LIM-Homeodomain Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D016133:Polymerase Chain Reaction; D051381:Rats; D012474:Salmon / Q000235:genetics; D014157:Transcription Factors
D017931:DNA Primers; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1