Transcriptional regulation of the human carboxyl ester lipase gene in THP-1 monocytes: an E-box required for activation binds upstream stimulatory factors 1 and 2.
The bile salt-stimulated carboxyl ester lipase (CEL) is important for the digestion and absorption of dietary lipids, and is expressed at high levels by the exocrine pancreas and the lactating mammary gland. However, the presence of CEL in human plasma suggests that the role of CEL in lipid metabolism may stretch beyond its function in the intestinal lumen, and possibly include interactions with cholesterol and oxidized lipoproteins to modulate the progression of atherosclerosis. We have used the CEL-expressing human monocytic cell line THP-1 to investigate the transcriptional regulation of the human CEL in monocytes. Analyses of the promoter region revealed that an E-box located at -47/-52 is necessary for CEL expression. Point mutations in the E-box almost completely abolish the transcriptional activity. Electrophoretic mobility-shift assay analyses reveal that the E-box binds the upstream stimulatory factors 1 and 2, and the binding of an upstream stimulatory factor-containing complex in THP-1 cells also requires the presence of a putative nuclear receptor-binding site at -60/-66. Furthermore, we demonstrate that the E-box is also necessary for CEL expression in the pancreas and the mammary gland, although there are tissue-specific requirements for additional activating elements.
Bengtsson
Sara H M
SH
Department of CMB/Molecular Biology, Box 462, S-405 30 Göteborg, Sweden. Sara.Bengtsson@molbio.gu.se
Madeyski-Bengtson
Katja
K
Nilsson
Jeanette
J
Bjursell
Gunnar
G
D000818:Animals; D001483:Base Sequence; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009000:Monocytes / Q000201:enzymology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D051720:Upstream Stimulatory Factors
D017931:DNA Primers; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase