Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 2000 Oct 15;351(Pt 2):367–376.

The tissue-specific regulation of the carboxyl ester lipase gene in exocrine pancreas differs significantly between mouse and human.

M Kannius-Janson 1, U Lidberg 1, G Bjursell 1, J Nilsson 1
PMCID: PMC1221372  PMID: 11023822

Abstract

The carboxyl ester lipase (CEL) gene is highly expressed in exocrine pancreas and expression of the human CEL gene is mediated by a strong tissue-specific enhancer, which is absolutely necessary for high-level expression. The mouse promoter, on the other hand, does not contain a corresponding enhancer element, but instead is totally dependent on another pancreas-specific element. This element is identified as a pancreatic transcription factor 1 (PTF 1)-binding site. The human CEL promoter also contains a putative PTF 1 element located at a position corresponding to the essential PTF 1 site in the mouse promoter. However, nucleotide changes in the human promoter 5' flanking this PTF 1 site have created an overlapping CCAAT/enhancer-binding protein (C/EBP)-like binding motif, interfering with the binding of PTF 1. Hence, our findings provide an example of genetic divergence between species not accompanied by difference in function.

Full Text

The Full Text of this article is available as a PDF (242.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  2. Carlsson P., Bjursell G. Negative and positive promoter elements contribute to tissue specificity of apolipoprotein B expression. Gene. 1989 Apr 15;77(1):113–121. doi: 10.1016/0378-1119(89)90365-x. [DOI] [PubMed] [Google Scholar]
  3. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  4. Cockell M., Stevenson B. J., Strubin M., Hagenbüchle O., Wellauer P. K. Identification of a cell-specific DNA-binding activity that interacts with a transcriptional activator of genes expressed in the acinar pancreas. Mol Cell Biol. 1989 Jun;9(6):2464–2476. doi: 10.1128/mcb.9.6.2464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cockell M., Stolarczyk D., Frutiger S., Hughes G. J., Hagenbüchle O., Wellauer P. K. Binding sites for hepatocyte nuclear factor 3 beta or 3 gamma and pancreas transcription factor 1 are required for efficient expression of the gene encoding pancreatic alpha-amylase. Mol Cell Biol. 1995 Apr;15(4):1933–1941. doi: 10.1128/mcb.15.4.1933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Delegeane A. M., Ferland L. H., Mellon P. L. Tissue-specific enhancer of the human glycoprotein hormone alpha-subunit gene: dependence on cyclic AMP-inducible elements. Mol Cell Biol. 1987 Nov;7(11):3994–4002. doi: 10.1128/mcb.7.11.3994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fukuoka S., Zhang D. E., Taniguchi Y., Scheele G. A. Structure of the canine pancreatic colipase gene includes two protein-binding sites in the promoter region. J Biol Chem. 1993 May 25;268(15):11312–11320. [PubMed] [Google Scholar]
  8. Kannius-Janson M., Lidberg U., Hultén K., Gritli-Linde A., Bjursell G., Nilsson J. Studies of the regulation of the mouse carboxyl ester lipase gene in mammary gland. Biochem J. 1998 Dec 15;336(Pt 3):577–585. doi: 10.1042/bj3360577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Krapp A., Knöfler M., Frutiger S., Hughes G. J., Hagenbüchle O., Wellauer P. K. The p48 DNA-binding subunit of transcription factor PTF1 is a new exocrine pancreas-specific basic helix-loop-helix protein. EMBO J. 1996 Aug 15;15(16):4317–4329. [PMC free article] [PubMed] [Google Scholar]
  10. Krapp A., Knöfler M., Ledermann B., Bürki K., Berney C., Zoerkler N., Hagenbüchle O., Wellauer P. K. The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas. Genes Dev. 1998 Dec 1;12(23):3752–3763. doi: 10.1101/gad.12.23.3752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kruse F., Rose S. D., Swift G. H., Hammer R. E., MacDonald R. J. An endocrine-specific element is an integral component of an exocrine-specific pancreatic enhancer. Genes Dev. 1993 May;7(5):774–786. doi: 10.1101/gad.7.5.774. [DOI] [PubMed] [Google Scholar]
  12. Kruse F., Rose S. D., Swift G. H., Hammer R. E., MacDonald R. J. Cooperation between elements of an organ-specific transcriptional enhancer in animals. Mol Cell Biol. 1995 Aug;15(8):4385–4394. doi: 10.1128/mcb.15.8.4385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lidberg U., Kannius-Janson M., Nilsson J., Bjursell G. Transcriptional regulation of the human carboxyl ester lipase gene in exocrine pancreas. Evidence for a unique tissue-specific enhancer. J Biol Chem. 1998 Nov 20;273(47):31417–31426. doi: 10.1074/jbc.273.47.31417. [DOI] [PubMed] [Google Scholar]
  14. Lidmer A. S., Kannius M., Lundberg L., Bjursell G., Nilsson J. Molecular cloning and characterization of the mouse carboxyl ester lipase gene and evidence for expression in the lactating mammary gland. Genomics. 1995 Sep 1;29(1):115–122. doi: 10.1006/geno.1995.1221. [DOI] [PubMed] [Google Scholar]
  15. Madeyski K., Lidberg U., Bjursell G., Nilsson J. Characterization of the gorilla carboxyl ester lipase locus, and the appearance of the carboxyl ester lipase pseudogene during primate evolution. Gene. 1999 Nov 1;239(2):273–282. doi: 10.1016/s0378-1119(99)00410-2. [DOI] [PubMed] [Google Scholar]
  16. Madeyski K., Lidberg U., Bjursell G., Nilsson J. Structure and organization of the human carboxyl ester lipase locus. Mamm Genome. 1998 Apr;9(4):334–338. doi: 10.1007/s003359900762. [DOI] [PubMed] [Google Scholar]
  17. Mullis P. E., Holl R. W., Lund T., Eblé A., Brickell P. M. Regulation of human growth hormone-binding protein production by human growth hormone in a hepatoma cell line. Mol Cell Endocrinol. 1995 Jun;111(2):181–190. doi: 10.1016/0303-7207(95)03567-q. [DOI] [PubMed] [Google Scholar]
  18. Ohlsson H., Thor S., Edlund T. Novel insulin promoter- and enhancer-binding proteins that discriminate between pancreatic alpha- and beta-cells. Mol Endocrinol. 1991 Jul;5(7):897–904. doi: 10.1210/mend-5-7-897. [DOI] [PubMed] [Google Scholar]
  19. Rose S. D., MacDonald R. J. Evolutionary silencing of the human elastase I gene (ELA1). Hum Mol Genet. 1997 Jun;6(6):897–903. doi: 10.1093/hmg/6.6.897. [DOI] [PubMed] [Google Scholar]
  20. Sims H. F., Lowe M. E. The human colipase gene: isolation, chromosomal location, and tissue-specific expression. Biochemistry. 1992 Aug 11;31(31):7120–7125. doi: 10.1021/bi00146a013. [DOI] [PubMed] [Google Scholar]
  21. Slack J. M. Developmental biology of the pancreas. Development. 1995 Jun;121(6):1569–1580. doi: 10.1242/dev.121.6.1569. [DOI] [PubMed] [Google Scholar]
  22. Smith W. C., Kuniyoshi J., Talamantes F. Mouse serum growth hormone (GH) binding protein has GH receptor extracellular and substituted transmembrane domains. Mol Endocrinol. 1989 Jun;3(6):984–990. doi: 10.1210/mend-3-6-984. [DOI] [PubMed] [Google Scholar]
  23. Swift G. H., Kruse F., MacDonald R. J., Hammer R. E. Differential requirements for cell-specific elastase I enhancer domains in transfected cells and transgenic mice. Genes Dev. 1989 May;3(5):687–696. doi: 10.1101/gad.3.5.687. [DOI] [PubMed] [Google Scholar]
  24. Swift G. H., Liu Y., Rose S. D., Bischof L. J., Steelman S., Buchberg A. M., Wright C. V., MacDonald R. J. An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2). Mol Cell Biol. 1998 Sep;18(9):5109–5120. doi: 10.1128/mcb.18.9.5109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Swift G. H., Rose S. D., MacDonald R. J. An element of the elastase I enhancer is an overlapping bipartite binding site activated by a heteromeric factor. J Biol Chem. 1994 Apr 29;269(17):12809–12815. [PubMed] [Google Scholar]
  26. Timchenko N., Wilson D. R., Taylor L. R., Abdelsayed S., Wilde M., Sawadogo M., Darlington G. J. Autoregulation of the human C/EBP alpha gene by stimulation of upstream stimulatory factor binding. Mol Cell Biol. 1995 Mar;15(3):1192–1202. doi: 10.1128/mcb.15.3.1192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yamaoka T., Itakura M. Development of pancreatic islets (review). Int J Mol Med. 1999 Mar;3(3):247–261. doi: 10.3892/ijmm.3.3.247. [DOI] [PubMed] [Google Scholar]
  28. el-Amraoui A., Sahly I., Picaud S., Sahel J., Abitbol M., Petit C. Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells. Hum Mol Genet. 1996 Aug;5(8):1171–1178. doi: 10.1093/hmg/5.8.1171. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES