Insulin-like growth factor binding protein-3. Organization of the human chromosomal gene and demonstration of promoter activity.
Insulin-like growth factor binding protein-3 (IGFBP-3) can modulate the mitogenic and metabolic effects of the insulin-like growth factors (IGFs). IGFBP-3 protein levels are developmentally regulated and influenced by a number of hormonal stimuli both in vitro and in vivo. As a first step toward understanding how hormonal and developmental factors regulate IGFBP-3 production, we are characterizing the human IGFBP-3 chromosomal gene and promoter. Southern analysis demonstrates a single copy of the IGFBP-3 gene in the human genome. This gene spans 8.9 kilobases; the protein-coding region is divided into four exons while a fifth exon contains the 3'-untranslated region. Primer extension studies locate the IGFBP-3 mRNA cap site 132 base pairs 5' to the ATG translation initiation codon. On the chromosomal gene, this cap site is located 30 base pairs 3' to the start of a TATA box and 97 base pairs 3' to a consensus GC upstream promoter element, an organization common to many eukaryotic promoters. When this potential IGFBP-3 promoter region is placed upstream to the chloramphenicol acetyltransferase reporter gene, it directs high-level production of chloramphenicol acetyltransferase in transfected COS-1 cells. These observations suggest an uncomplicated organization for the IGFBP-3 chromosomal gene and promoter in the human genome.
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Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77054.
Suwanichkul
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Powell
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D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005796:Genes; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007438:Introns; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D013002:Somatomedins
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D004247:DNA