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Mol Cell Biol. Aug 1995; 15(8): 4385–4394.
PMCID: PMC230678

Cooperation between elements of an organ-specific transcriptional enhancer in animals.

Abstract

The elastase I gene enhancer that specifies high levels of pancreatic transcription comprises three functional elements (A, B, and C). When assayed individually in transgenic mice, homomultimers of A are acinar cell specific, those of B are islet specific, and those of C are inactive. To determine how the elements interact in the elastase I enhancer and to investigate further the role of the C element, we have examined the activity of the three possible combinations of synthetic double elements in transgenic animals. Combining the A and B elements reconstitutes the exocrine plus endocrine specificity of the intact enhancer with an increased activity in acinar cells compared with that in the A homomultimer. The B element therefore plays a dual role: in islet cells it is capable of activating transcription, whereas in acinar cells it is inactive alone but greatly augments the activity specified by the A element. The C element augments the activity of either the A or B element without affecting their pancreatic cell type specificity. The roles of each element were verified by examining the effects of mutational inactivation of each element within the context of the elastase I enhancer. These results demonstrated that when tested in animals, the individual enhancer elements can perform discrete, separable functions that combine additively for cell type specificity and cooperatively for the overall strength of a multielement stage- and site-specific transcriptional enhancer.

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Selected References

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  • Bailey JM, Davidson N. Methylmercury as a reversible denaturing agent for agarose gel electrophoresis. Anal Biochem. 1976 Jan;70(1):75–85. [PubMed]
  • Boulet AM, Erwin CR, Rutter WJ. Cell-specific enhancers in the rat exocrine pancreas. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3599–3603. [PMC free article] [PubMed]
  • Brinster RL, Chen HY, Trumbauer ME, Yagle MK, Palmiter RD. Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4438–4442. [PMC free article] [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Cockell M, Stevenson BJ, Strubin M, Hagenbüchle O, Wellauer PK. 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. [PMC free article] [PubMed]
  • Davis BP, Hammer RE, Messing A, MacDonald RJ. Selective expression of trypsin fusion genes in acinar cells of the pancreas and stomach of transgenic mice. J Biol Chem. 1992 Dec 25;267(36):26070–26077. [PubMed]
  • Guz Y, Montminy MR, Stein R, Leonard J, Gamer LW, Wright CV, Teitelman G. Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny. Development. 1995 Jan;121(1):11–18. [PubMed]
  • Hammer RE, Swift GH, Ornitz DM, Quaife CJ, Palmiter RD, Brinster RL, MacDonald RJ. The rat elastase I regulatory element is an enhancer that directs correct cell specificity and developmental onset of expression in transgenic mice. Mol Cell Biol. 1987 Aug;7(8):2956–2967. [PMC free article] [PubMed]
  • Han JH, Rall L, Rutter WJ. Selective expression of rat pancreatic genes during embryonic development. Proc Natl Acad Sci U S A. 1986 Jan;83(1):110–114. [PMC free article] [PubMed]
  • Howard G, Keller PR, Johnson TM, Meisler MH. Binding of a pancreatic nuclear protein is correlated with amylase enhancer activity. Nucleic Acids Res. 1989 Oct 25;17(20):8185–8195. [PMC free article] [PubMed]
  • Jonsson J, Carlsson L, Edlund T, Edlund H. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature. 1994 Oct 13;371(6498):606–609. [PubMed]
  • Kedzierski W, Porter JC. A novel non-enzymatic procedure for removing DNA template from RNA transcription mixtures. Biotechniques. 1991 Feb;10(2):210–214. [PubMed]
  • Kruse F, Komro CT, Michnoff CH, MacDonald RJ. The cell-specific elastase I enhancer comprises two domains. Mol Cell Biol. 1988 Feb;8(2):893–902. [PMC free article] [PubMed]
  • Kruse F, Rose SD, Swift GH, Hammer RE, MacDonald RJ. An endocrine-specific element is an integral component of an exocrine-specific pancreatic enhancer. Genes Dev. 1993 May;7(5):774–786. [PubMed]
  • Leonard J, Peers B, Johnson T, Ferreri K, Lee S, Montminy MR. Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells. Mol Endocrinol. 1993 Oct;7(10):1275–1283. [PubMed]
  • MacDonald RJ. Expression of the pancreatic elastase I gene in transgenic mice. Hepatology. 1987 Jan-Feb;7(1 Suppl):42S–51S. [PubMed]
  • MacDonald RJ, Swift GH, Przybyla AE, Chirgwin JM. Isolation of RNA using guanidinium salts. Methods Enzymol. 1987;152:219–227. [PubMed]
  • Meister A, Weinrich SL, Nelson C, Rutter WJ. The chymotrypsin enhancer core. Specific factor binding and biological activity. J Biol Chem. 1989 Dec 5;264(34):20744–20751. [PubMed]
  • Miller CP, McGehee RE, Jr, Habener JF. IDX-1: a new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene. EMBO J. 1994 Mar 1;13(5):1145–1156. [PMC free article] [PubMed]
  • Ohlsson H, Karlsson K, Edlund T. IPF1, a homeodomain-containing transactivator of the insulin gene. EMBO J. 1993 Nov;12(11):4251–4259. [PMC free article] [PubMed]
  • Ornitz DM, Hammer RE, Davison BL, Brinster RL, Palmiter RD. Promoter and enhancer elements from the rat elastase I gene function independently of each other and of heterologous enhancers. Mol Cell Biol. 1987 Oct;7(10):3466–3472. [PMC free article] [PubMed]
  • Ornitz DM, Palmiter RD, Hammer RE, Brinster RL, Swift GH, MacDonald RJ. Specific expression of an elastase-human growth hormone fusion gene in pancreatic acinar cells of transgenic mice. Nature. 1985 Feb 14;313(6003):600–602. [PubMed]
  • Osborn L, Rosenberg MP, Keller SA, Meisler MH. Tissue-specific and insulin-dependent expression of a pancreatic amylase gene in transgenic mice. Mol Cell Biol. 1987 Jan;7(1):326–334. [PMC free article] [PubMed]
  • Peshavaria M, Gamer L, Henderson E, Teitelman G, Wright CV, Stein R. XIHbox 8, an endoderm-specific Xenopus homeodomain protein, is closely related to a mammalian insulin gene transcription factor. Mol Endocrinol. 1994 Jun;8(6):806–816. [PubMed]
  • Petrucco S, Wellauer PK, Hagenbüchle O. The DNA-binding activity of transcription factor PTF1 parallels the synthesis of pancreas-specific mRNAs during mouse development. Mol Cell Biol. 1990 Jan;10(1):254–264. [PMC free article] [PubMed]
  • Reeder RH. Enhancers and ribosomal gene spacers. Cell. 1984 Sep;38(2):349–351. [PubMed]
  • Rose SD, Kruse F, Swift GH, MacDonald RJ, Hammer RE. A single element of the elastase I enhancer is sufficient to direct transcription selectively to the pancreas and gut. Mol Cell Biol. 1994 Mar;14(3):2048–2057. [PMC free article] [PubMed]
  • Roux E, Strubin M, Hagenbüchle O, Wellauer PK. The cell-specific transcription factor PTF1 contains two different subunits that interact with the DNA. Genes Dev. 1989 Oct;3(10):1613–1624. [PubMed]
  • Scott V, Clark AR, Hutton JC, Docherty K. Two proteins act as the IUF1 insulin gene enhancer binding factor. FEBS Lett. 1991 Sep 23;290(1-2):27–30. [PubMed]
  • Seeburg PH. The human growth hormone gene family: nucleotide sequences show recent divergence and predict a new polypeptide hormone. DNA. 1982;1(3):239–249. [PubMed]
  • Stevenson BJ, Hagenbüchle O, Wellauer PK. Sequence organisation and transcriptional regulation of the mouse elastase II and trypsin genes. Nucleic Acids Res. 1986 Nov 11;14(21):8307–8330. [PMC free article] [PubMed]
  • Swift GH, Craik CS, Stary SJ, Quinto C, Lahaie RG, Rutter WJ, MacDonald RJ. Structure of the two related elastase genes expressed in the rat pancreas. J Biol Chem. 1984 Nov 25;259(22):14271–14278. [PubMed]
  • Swift GH, Kruse F, MacDonald RJ, Hammer RE. Differential requirements for cell-specific elastase I enhancer domains in transfected cells and transgenic mice. Genes Dev. 1989 May;3(5):687–696. [PubMed]
  • Swift GH, Rose SD, MacDonald RJ. 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]
  • Weinrich SL, Meister A, Rutter WJ. Exocrine pancreas transcription factor 1 binds to a bipartite enhancer element and activates transcription of acinar genes. Mol Cell Biol. 1991 Oct;11(10):4985–4997. [PMC free article] [PubMed]
  • Weintraub H. Formation of stable transcription complexes as assayed by analysis of individual templates. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5819–5823. [PMC free article] [PubMed]

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