A single element of the elastase I enhancer is sufficient to direct transcription selectively to the pancreas and gut.
The elastase I (EI) gene is expressed at high levels in the exocrine pancreas and at lower levels in other regions of the gut. The transcriptional enhancer of the EI gene, from nucleotides -205 to -72, recapitulates the expression of the endogenous gene in transgenic mice; it directs not only pancreatic acinar cell expression of a human growth hormone (hGH) transgene but also expression to the stomach, duodenum, and colon. This pattern of selective expression limited to the gastroenteropancreatic organ system is specified by the A element, one of three functional elements in the EI enhancer. When multimerized, the A element directed expression of a hGH reporter gene selectively to the pancreas, stomach, and intestine in transgenic mice. Immunofluorescent localization of hGH indicated that the A element multimer transgenes were expressed in the acinar cells of the pancreas as well as in Brunner's gland cells of the duodenum. The A element binds a pancreatic acinar cell-specific factor, PTF1. Our results show that while the A element is responsible for directing tissue and cell type specificity, other elements of the enhancer must be involved in the regulation of the level of gene expression.
Rose
S D
SD
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9038.
Kruse
F
F
Swift
G H
GH
MacDonald
R J
RJ
Hammer
R E
RE
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004742:Enhancer Elements, Genetic; D015971:Gene Expression Regulation, Enzymologic; D007422:Intestines / Q000201:enzymology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010179:Pancreas / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014157:Transcription Factors; C062602:transcription factor PTF1; D010196:Pancreatic Elastase