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Proc Natl Acad Sci U S A. Dec 15, 1991; 88(24): 11495–11499.
PMCID: PMC53162

The E-cadherin promoter: functional analysis of a G.C-rich region and an epithelial cell-specific palindromic regulatory element.

Abstract

The cell-cell adhesion molecule E-cadherin is specifically expressed in epithelia and is involved in the maintenance of the epithelial phenotype. Expression of E-cadherin is downregulated in many poorly differentiated carcinomas, which leads to higher motility and invasiveness of the cells. To examine the mechanisms that regulate tissue-specific expression, we have characterized the promoter of the E-cadherin gene. We found that an upstream fragment (positions -178 to +92) mediates strong expression of a chloramphenicol acetyltransferase reporter gene in epithelial cells (i.e., 60% of the level obtained with simian virus 40 promoter/enhancer constructs), whereas in nonepithelial cells this promoter was either inactive or much less active. By DNase I footprinting and gel retardation analysis as well as through functional dissection of the regulatory sequences, we identified two regions that contribute to tissue-specific activity of the promoter: (i) a G-C-rich region between -25 and -58 that generates basic epithelial promoter activity, most likely in combination with an "initiator" element present at the single transcription start site of the gene, and (ii) a palindromic sequence between -75 and -86 (named E-pal) that potentiates the activity of the proximal E-cadherin promoter and confers epithelial cell-specific activity on a simian virus 40 promoter. The E-pal sequence is homologous to cis regulatory elements active in keratin gene promoters and competes with these elements for nuclear factor binding. Interestingly, the activity of the E-cadherin promoter was reduced in dedifferentiated breast carcinoma cells, indicating that the identified elements are subject to negative regulation during tumor progression.

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Selected References

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  • Rodriguez-Boulan E, Nelson WJ. Morphogenesis of the polarized epithelial cell phenotype. Science. 1989 Aug 18;245(4919):718–725. [PubMed]
  • Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991 Mar 22;251(5000):1451–1455. [PubMed]
  • Behrens J, Birchmeier W, Goodman SL, Imhof BA. Dissociation of Madin-Darby canine kidney epithelial cells by the monoclonal antibody anti-arc-1: mechanistic aspects and identification of the antigen as a component related to uvomorulin. J Cell Biol. 1985 Oct;101(4):1307–1315. [PMC free article] [PubMed]
  • Behrens J, Mareel MM, Van Roy FM, Birchmeier W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol. 1989 Jun;108(6):2435–2447. [PMC free article] [PubMed]
  • Gumbiner B, Simons K. A functional assay for proteins involved in establishing an epithelial occluding barrier: identification of a uvomorulin-like polypeptide. J Cell Biol. 1986 Feb;102(2):457–468. [PMC free article] [PubMed]
  • Nagafuchi A, Shirayoshi Y, Okazaki K, Yasuda K, Takeichi M. Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA. Nature. 1987 Sep 24;329(6137):341–343. [PubMed]
  • Mege RM, Matsuzaki F, Gallin WJ, Goldberg JI, Cunningham BA, Edelman GM. Construction of epithelioid sheets by transfection of mouse sarcoma cells with cDNAs for chicken cell adhesion molecules. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7274–7278. [PMC free article] [PubMed]
  • Ringwald M, Schuh R, Vestweber D, Eistetter H, Lottspeich F, Engel J, Dölz R, Jähnig F, Epplen J, Mayer S, et al. The structure of cell adhesion molecule uvomorulin. Insights into the molecular mechanism of Ca2+-dependent cell adhesion. EMBO J. 1987 Dec 1;6(12):3647–3653. [PMC free article] [PubMed]
  • Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, Löchner D, Birchmeier W. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991 Apr;113(1):173–185. [PMC free article] [PubMed]
  • Gorman CM, Moffat LF, Howard BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. [PMC free article] [PubMed]
  • Ryffel GU, Kugler W, Wagner U, Kaling M. Liver cell specific gene transcription in vitro: the promoter elements HP1 and TATA box are necessary and sufficient to generate a liver-specific promoter. Nucleic Acids Res. 1989 Feb 11;17(3):939–953. [PMC free article] [PubMed]
  • Klein-Hitpass L, Tsai SY, Greene GL, Clark JH, Tsai MJ, O'Malley BW. Specific binding of estrogen receptor to the estrogen response element. Mol Cell Biol. 1989 Jan;9(1):43–49. [PMC free article] [PubMed]
  • Leask A, Rosenberg M, Vassar R, Fuchs E. Regulation of a human epidermal keratin gene: sequences and nuclear factors involved in keratinocyte-specific transcription. Genes Dev. 1990 Nov;4(11):1985–1998. [PubMed]
  • Imagawa M, Chiu R, Karin M. Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. Cell. 1987 Oct 23;51(2):251–260. [PubMed]
  • Snape AM, Jonas EA, Sargent TD. KTF-1, a transcriptional activator of Xenopus embryonic keratin expression. Development. 1990 May;109(1):157–165. [PubMed]
  • Hennighausen L, Lubon H. Interaction of protein with DNA in vitro. Methods Enzymol. 1987;152:721–735. [PubMed]
  • Smale ST, Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. [PubMed]
  • Smale ST, Schmidt MC, Berk AJ, Baltimore D. Transcriptional activation by Sp1 as directed through TATA or initiator: specific requirement for mammalian transcription factor IID. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4509–4513. [PMC free article] [PubMed]
  • Mitchell PJ, Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. [PubMed]
  • Dynan WS. Modularity in promoters and enhancers. Cell. 1989 Jul 14;58(1):1–4. [PubMed]
  • Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. [PubMed]
  • Mitchell PJ, Timmons PM, Hébert JM, Rigby PW, Tjian R. Transcription factor AP-2 is expressed in neural crest cell lineages during mouse embryogenesis. Genes Dev. 1991 Jan;5(1):105–119. [PubMed]
  • Weintraub H, Davis R, Tapscott S, Thayer M, Krause M, Benezra R, Blackwell TK, Turner D, Rupp R, Hollenberg S, et al. The myoD gene family: nodal point during specification of the muscle cell lineage. Science. 1991 Feb 15;251(4995):761–766. [PubMed]
  • Kageyama R, Merlino GT, Pastan I. Nuclear factor ETF specifically stimulates transcription from promoters without a TATA box. J Biol Chem. 1989 Sep 15;264(26):15508–15514. [PubMed]
  • Kageyama R, Pastan I. Molecular cloning and characterization of a human DNA binding factor that represses transcription. Cell. 1989 Dec 1;59(5):815–825. [PubMed]

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