Transcriptional regulation of the human carboxyl ester lipase gene in exocrine pancreas. Evidence for a unique tissue-specific enhancer.
The human carboxyl ester lipase (CEL) is an important enzyme for the intestinal absorption of dietary lipids. The gene is highly expressed in exocrine pancreas and in the mammary gland during pregnancy and lactation. In this paper, we have focused on its transcriptional regulation in exocrine pancreas. Reporter gene analysis in cell cultures reveals that a high level of tissue-specific expression is established by the proximal 839 base pairs of the 5'-flanking region. This is due to a strong enhancer, located at -672 to -637. Transfections in mammary gland-derived cells reveal that the enhancer is pancreas-specific and does not contribute to the mammary gland expression. This indicates that the expression of the CEL gene in the mammary gland and pancreas, respectively, is due to two different regulatory systems. Further characterizations of the enhancer reveal that it is composed of two closely located cis-elements. The proximal element mediates a positive effect, whereas the distal element exerts a silencing effect on the positive proximal element. The functional enhancer complex is composed of ubiquitously expressed factors, since similar interactions are achieved with nuclear extracts from cells derived from other tissues. However, no enhancer activity is achieved in such cells. Hence, the net enhancer activity is the result of a tissue-specific balance between factors interacting with the two elements. Since none of the described cis-elements show any clear homology to known cis-elements, we propose that the interacting complex is composed of yet unidentified transcription factors.
Lidberg
U
U
Department of Molecular Biology, Göteborg 40 530, Sweden. ulf.lidberg@molbio.gu.se
Kannius-Janson
M
M
Nilsson
J
J
Bjursell
G
G
D001483:Base Sequence; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010179:Pancreas / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements; D017384:Sequence Deletion; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase