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. 1995 May 25;23(10):1717–1721. doi: 10.1093/nar/23.10.1717

A gene-type-specific enhancer regulates the carbamyl phosphate synthetase I promoter by cooperating with the proximal GAG activating element.

I S Goping 1, S Lamontagne 1, G C Shore 1, M Nguyen 1
PMCID: PMC306927  PMID: 7784176

Abstract

The rat carbamyl phosphate synthetase I gene is expressed in two cell types: hepatocytes and epithelial cells of the intestinal mucosa. The proximal promoter contains a single activating element, GAG, two repressor elements (sites I and III) and an anti-repressor element (site II). Although these elements together exhibit the potential for complex regulation, they are unable to confer tissue-specific promoter activity. Here we have identified a cell-type-specific enhancer that lies 10 kilobases upstream of the promoter. Unexpectedly, the enhancer also functioned in a gene-type-specific manner. The enhancer stimulated promoter activity exclusively through the proximal GAG element. Abrogation of GAG, either directly by mutation of GAG or indirectly by sites I and III repressors, abolished enhancer activation. Conversely, activation of the heterologous thymidine kinase promoter by the enhancer required the introduction of GAG. The requirement for GAG, therefore, functions to constrain the enhancer to a specific target promoter.

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Selected References

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

  1. Artandi S. E., Cooper C., Shrivastava A., Calame K. The basic helix-loop-helix-zipper domain of TFE3 mediates enhancer-promoter interaction. Mol Cell Biol. 1994 Dec;14(12):7704–7716. doi: 10.1128/mcb.14.12.7704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Banville D., Boie Y. Retroviral long terminal repeat is the promoter of the gene encoding the tumor-associated calcium-binding protein oncomodulin in the rat. J Mol Biol. 1989 Jun 5;207(3):481–490. doi: 10.1016/0022-2836(89)90458-0. [DOI] [PubMed] [Google Scholar]
  3. Bonifer C., Hecht A., Saueressig H., Winter D. M., Sippel A. E. Dynamic chromatin: the regulatory domain organization of eukaryotic gene loci. J Cell Biochem. 1991 Oct;47(2):99–108. doi: 10.1002/jcb.240470203. [DOI] [PubMed] [Google Scholar]
  4. Eissenberg J. C., Elgin S. C. Boundary functions in the control of gene expression. Trends Genet. 1991 Oct;7(10):335–340. doi: 10.1016/0168-9525(91)90424-o. [DOI] [PubMed] [Google Scholar]
  5. Fahrner J., Labruyere W. T., Gaunitz C., Moorman A. F., Gebhardt R., Lamers W. H. Identification and functional characterization of regulatory elements of the glutamine synthetase gene from rat liver. Eur J Biochem. 1993 May 1;213(3):1067–1073. doi: 10.1111/j.1432-1033.1993.tb17854.x. [DOI] [PubMed] [Google Scholar]
  6. Goping I. S., Lagacé M., Shore G. C. Factors interacting with the rat carbamyl phosphate synthetase promoter in expressing and nonexpressing tissues. Gene. 1992 Sep 10;118(2):283–287. doi: 10.1016/0378-1119(92)90201-y. [DOI] [PubMed] [Google Scholar]
  7. Goping I. S., Shore G. C. Interactions between repressor and anti-repressor elements in the carbamyl phosphate synthetase I promoter. J Biol Chem. 1994 Feb 4;269(5):3891–3896. [PubMed] [Google Scholar]
  8. Howell B. W., Lagacé M., Shore G. C. Activity of the carbamyl phosphate synthetase I promoter in liver nuclear extracts is dependent on a cis-acting C/EBP recognition element. Mol Cell Biol. 1989 Jul;9(7):2928–2933. doi: 10.1128/mcb.9.7.2928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hu J. M., Camper S. A., Tilghman S. M., Miller T., Georgoff I., Serra R., Isom H. C. Functional analyses of albumin expression in a series of hepatocyte cell lines and in primary hepatocytes. Cell Growth Differ. 1992 Sep;3(9):577–588. [PubMed] [Google Scholar]
  10. Kellum R., Schedl P. A group of scs elements function as domain boundaries in an enhancer-blocking assay. Mol Cell Biol. 1992 May;12(5):2424–2431. doi: 10.1128/mcb.12.5.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lagacé M., Goping I. S., Mueller C. R., Lazzaro M., Shore G. C. The carbamyl phosphate synthetase promoter contains multiple binding sites for C/EBP-related proteins. Gene. 1992 Sep 10;118(2):231–238. doi: 10.1016/0378-1119(92)90193-s. [DOI] [PubMed] [Google Scholar]
  12. Lagacé M., Howell B. W., Burak R., Lusty C. J., Shore G. C. Rat carbamyl-phosphate synthetase I gene. Promoter sequence and tissue-specific transcriptional regulation in vitro. J Biol Chem. 1987 Aug 5;262(22):10415–10418. [PubMed] [Google Scholar]
  13. Li X., Noll M. Compatibility between enhancers and promoters determines the transcriptional specificity of gooseberry and gooseberry neuro in the Drosophila embryo. EMBO J. 1994 Jan 15;13(2):400–406. doi: 10.1002/j.1460-2075.1994.tb06274.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McKnight S. L., Gavis E. R., Kingsbury R., Axel R. Analysis of transcriptional regulatory signals of the HSV thymidine kinase gene: identification of an upstream control region. Cell. 1981 Aug;25(2):385–398. doi: 10.1016/0092-8674(81)90057-x. [DOI] [PubMed] [Google Scholar]
  15. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  16. Nitsch D., Schütz G. The distal enhancer implicated in the developmental regulation of the tyrosine aminotransferase gene is bound by liver-specific and ubiquitous factors. Mol Cell Biol. 1993 Aug;13(8):4494–4504. doi: 10.1128/mcb.13.8.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. O'Kane C. J., Gehring W. J. Detection in situ of genomic regulatory elements in Drosophila. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9123–9127. doi: 10.1073/pnas.84.24.9123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ptashne M., Gann A. A. Activators and targets. Nature. 1990 Jul 26;346(6282):329–331. doi: 10.1038/346329a0. [DOI] [PubMed] [Google Scholar]
  19. Roeder R. G. The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly. Trends Biochem Sci. 1991 Nov;16(11):402–408. doi: 10.1016/0968-0004(91)90164-q. [DOI] [PubMed] [Google Scholar]
  20. Ryall J., Nguyen M., Bendayan M., Shore G. C. Expression of nuclear genes encoding the urea cycle enzymes, carbamoyl-phosphate synthetase I and ornithine carbamoyl transferase, in rat liver and intestinal mucosa. Eur J Biochem. 1985 Oct 15;152(2):287–292. doi: 10.1111/j.1432-1033.1985.tb09196.x. [DOI] [PubMed] [Google Scholar]
  21. Weber F., de Villiers J., Schaffner W. An SV40 "enhancer trap" incorporates exogenous enhancers or generates enhancers from its own sequences. Cell. 1984 Apr;36(4):983–992. doi: 10.1016/0092-8674(84)90048-5. [DOI] [PubMed] [Google Scholar]

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