The human colipase gene: isolation, chromosomal location, and tissue-specific expression.
The digestion of dietary triglycerides occurs in the duodenum through the action of triglyceride lipase, a pancreatic exocrine protein. The activity of pancreatic lipase is inhibited by the bile salts normally found in the gut lumen. Another pancreatic exocrine protein, colipase, restores the lipolytic activity of triglyceride lipase. The synthesis and secretion of both triglyceride lipase and colipase is increased by dietary fats and secretin. An increase in mRNA accompanies the increased activity, suggesting that the genes for triglyceride lipase and colipase contain nucleotide elements responsive to dietary fats or secretin or both. To study the regulation of colipase expression, we have first isolated the gene for human colipase from a cosmid library with a cDNA probe. The gene was localized to chromosome 6 and is organized into three exons contained in a single 3.3-kb BamHI fragment. The 5'-flanking region of the gene contains a TATA box, a GC box, and a 28-bp region with homology to the rat pancreatic-specific enhancer. This region directs the tissue-specific expression of the chloramphenicol acetyltransferase gene in a transfected rat pancreatic acinar cell line, AR42-J. The same construct is inactive in HEPG2, C2C12, and COS-1 cells. These results demonstrate that the isolated gene for human colipase contains tissue-specific promoter activity in the 5'-flanking DNA. The 28-bp region specifically binds to a factor in nuclear extracts.
Sims
H F
HF
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63101.
Lowe
M E
ME
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003089:Colipases / Q000235:genetics*; D006224:Cricetinae; D004247:DNA; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D006822:Hybrid Cells; D008969:Molecular Sequence Data; D016385:TATA Box; D014162:Transfection
D003089:Colipases; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase