• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Aug 1987; 7(8): 2956–2967.
PMCID: PMC367915

The rat elastase I regulatory element is an enhancer that directs correct cell specificity and developmental onset of expression in transgenic mice.

Abstract

A total of 134 base pairs of the 5' flanking sequence of the elastase I gene is sufficient and necessary to direct expression of the passive human growth hormone gene (hGH) to the exocrine pancreas. We demonstrate that this elastase I regulatory region contains a transcriptional enhancer which directs acinar cell-specific expression in transgenic animals. The elastase I enhancer specifies correct expression of the linked hGH gene in an orientation- and position-independent manner and can activate a heterologous promoter. The enhancer also directs the appropriate temporal activation of the hGH gene in the developing pancreas. Transcription is initiated correctly for the elastase I or hGH promoter, and the transcripts are correctly processed regardless of the enhancer position within or outside the fusion gene. The elastase I enhancer generates coincident DNase I-hypersensitive sites in pancreatic chromatin when moved 3 kilobases upstream or within the first intron of the hGH gene and when associated with the hGH promoter.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aviv H, Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. [PMC free article] [PubMed]
  • Banerji J, Olson L, Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. [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]
  • Brinster RL, Ritchie KA, Hammer RE, O'Brien RL, Arp B, Storb U. Expression of a microinjected immunoglobulin gene in the spleen of transgenic mice. Nature. 1983 Nov 24;306(5941):332–336. [PubMed]
  • Burch JB, Weintraub H. Temporal order of chromatin structural changes associated with activation of the major chicken vitellogenin gene. Cell. 1983 May;33(1):65–76. [PubMed]
  • Chada K, Magram J, Raphael K, Radice G, Lacy E, Costantini F. Specific expression of a foreign beta-globin gene in erythroid cells of transgenic mice. Nature. 314(6009):377–380. [PubMed]
  • Chen CW, Thomas CA., Jr Recovery of DNA segments from agarose gels. Anal Biochem. 1980 Jan 15;101(2):339–341. [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Durnam DM, Palmiter RD. A practical approach for quantitating specific mRNAs by solution hybridization. Anal Biochem. 1983 Jun;131(2):385–393. [PubMed]
  • Eissenberg JC, Cartwright IL, Thomas GH, Elgin SC. Selected topics in chromatin structure. Annu Rev Genet. 1985;19:485–536. [PubMed]
  • Emerson BM, Lewis CD, Felsenfeld G. Interaction of specific nuclear factors with the nuclease-hypersensitive region of the chicken adult beta-globin gene: nature of the binding domain. Cell. 1985 May;41(1):21–30. [PubMed]
  • Fritton HP, Igo-Kemenes T, Nowock J, Strech-Jurk U, Theisen M, Sippel AE. Alternative sets of DNase I-hypersensitive sites characterize the various functional states of the chicken lysozyme gene. Nature. 1984 Sep 13;311(5982):163–165. [PubMed]
  • Geck P, Nász I. Concentrated, digestible DNA after hydroxylapatite chromatography with cetylpyridinium bromide precipitation. Anal Biochem. 1983 Dec;135(2):264–268. [PubMed]
  • Gillies SD, Morrison SL, Oi VT, Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983 Jul;33(3):717–728. [PubMed]
  • Hammer RE, Krumlauf R, Camper SA, Brinster RL, Tilghman SM. Diversity of alpha-fetoprotein gene expression in mice is generated by a combination of separate enhancer elements. Science. 1987 Jan 2;235(4784):53–58. [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]
  • Hanahan D. Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature. 1985 May 9;315(6015):115–122. [PubMed]
  • Jongstra J, Reudelhuber TL, Oudet P, Benoist C, Chae CB, Jeltsch JM, Mathis DJ, Chambon P. Induction of altered chromatin structures by simian virus 40 enhancer and promoter elements. Nature. 1984 Feb 23;307(5953):708–714. [PubMed]
  • Krumlauf R, Hammer RE, Tilghman SM, Brinster RL. Developmental regulation of alpha-fetoprotein genes in transgenic mice. Mol Cell Biol. 1985 Jul;5(7):1639–1648. [PMC free article] [PubMed]
  • MacDonald RJ, Hammer RE, Swift GH, Davis BP, Brinster RL. Transgenic progeny inherit tissue-specific expression of rat elastase I genes. DNA. 1986 Oct;5(5):393–401. [PubMed]
  • MacDonald RJ, Swift GH, Quinto C, Swain W, Pictet RL, Nikovits W, Rutter WJ. Primary structure of two distinct rat pancreatic preproelastases determined by sequence analysis of the complete cloned messenger ribonucleic acid sequences. Biochemistry. 1982 Mar 16;21(6):1453–1463. [PubMed]
  • Magram J, Chada K, Costantini F. Developmental regulation of a cloned adult beta-globin gene in transgenic mice. Nature. 1985 May 23;315(6017):338–340. [PubMed]
  • Maxam AM, Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. [PubMed]
  • Mulvihill ER, Palmiter RD. Relationship of nuclear estrogen receptor levels to induction of ovalbumin and conalbumin mRNA in chick oviduct. J Biol Chem. 1977 Mar 25;252(6):2060–2068. [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]
  • Ornitz DM, Palmiter RD, Messing A, Hammer RE, Pinkert CA, Brinster RL. Elastase I promoter directs expression of human growth hormone and SV40 T antigen genes to pancreatic acinar cells in transgenic mice. Cold Spring Harb Symp Quant Biol. 1985;50:399–409. [PubMed]
  • Overbeek PA, Chepelinsky AB, Khillan JS, Piatigorsky J, Westphal H. Lens-specific expression and developmental regulation of the bacterial chloramphenicol acetyltransferase gene driven by the murine alpha A-crystallin promoter in transgenic mice. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7815–7819. [PMC free article] [PubMed]
  • Palmiter RD, Brinster RL. Germ-line transformation of mice. Annu Rev Genet. 1986;20:465–499. [PubMed]
  • Palmiter RD, Norstedt G, Gelinas RE, Hammer RE, Brinster RL. Metallothionein-human GH fusion genes stimulate growth of mice. Science. 1983 Nov 18;222(4625):809–814. [PubMed]
  • Quaife CJ, Pinkert CA, Ornitz DM, Palmiter RD, Brinster RL. Pancreatic neoplasia induced by ras expression in acinar cells of transgenic mice. Cell. 1987 Mar 27;48(6):1023–1034. [PubMed]
  • Radice G, Costantini F. Tissue-specific DNase I hypersensitive sites in a foreign globin gene in transgenic mice. Nucleic Acids Res. 1986 Dec 22;14(24):9765–9780. [PMC free article] [PubMed]
  • Rutter WJ, Kemp JD, Bradshaw WS, Clark WR, Ronzio RA, Sanders TG. Regulation of specific protein synthesis in cytodifferentiation. J Cell Physiol. 1968 Oct;72(2 Suppl):1–18. [PubMed]
  • Schick J, Kern H, Scheele G. Hormonal stimulation in the exocrine pancreas results in coordinate and anticoordinate regulation of protein synthesis. J Cell Biol. 1984 Nov;99(5):1569–1574. [PMC free article] [PubMed]
  • Schick J, Verspohl R, Kern H, Scheele G. Two distinct adaptive responses in the synthesis of exocrine pancreatic enzymes to inverse changes in protein and carbohydrate in the diet. Am J Physiol. 1984 Dec;247(6 Pt 1):G611–G616. [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]
  • Shani M. Tissue-specific expression of rat myosin light-chain 2 gene in transgenic mice. Nature. 1985 Mar 21;314(6008):283–286. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [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, Hammer RE, MacDonald RJ, Brinster RL. Tissue-specific expression of the rat pancreatic elastase I gene in transgenic mice. Cell. 1984 Oct;38(3):639–646. [PubMed]
  • Townes TM, Lingrel JB, Chen HY, Brinster RL, Palmiter RD. Erythroid-specific expression of human beta-globin genes in transgenic mice. EMBO J. 1985 Jul;4(7):1715–1723. [PMC free article] [PubMed]
  • Walker MD, Edlund T, Boulet AM, Rutter WJ. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. [PubMed]
  • Wasylyk B, Wasylyk C, Chambon P. Short and long range activation by the SV40 enhancer. Nucleic Acids Res. 1984 Jul 25;12(14):5589–5608. [PMC free article] [PubMed]
  • Wilkie TM, Brinster RL, Palmiter RD. Germline and somatic mosaicism in transgenic mice. Dev Biol. 1986 Nov;118(1):9–18. [PubMed]
  • Van Nest GA, MacDonald RJ, Raman RK, Rutter WJ. Proteins synthesized and secreted during rat pancreatic development. J Cell Biol. 1980 Sep;86(3):784–794. [PMC free article] [PubMed]
  • Zassenhaus HP, Butow RA, Hannon YP. Rapid electroelution of nucleic acids from agarose and acrylamide gels. Anal Biochem. 1982 Sep 1;125(1):125–130. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...