Role of the αA-Crybp1 Site in Lens-Specific Expression of the αA-Crystallin Gene

  • Christina M. Sax
  • John F. Klement
  • Joram Piatigorsky


A heterogeneous group of crystallins comprise 80–90% of the soluble protein of the ocular lens and are responsible for lens transparency (see 30 for review). The two a-crystallins (αA and (αB) are present in all vertebrates, and arose from duplication of a common ancestral gene. The αA gene is expressed in a lens-specific manner, while the αB gene is expressed in numerous tissues (see 24 for review). A combination of transgenic mouse (28), mutagenesis, and cDNA cloning experiments (20) have implicated the αA-CRYBP1 site (5′- GGGAAATCCC-3′ at-66 to-57) in the lens-specific expression of the mouse α-crystallin gene.


Rous Sarcoma Virus Lens Epithelium Chloramphenicol Acetyltransferase Gene Chicken Lens Lens Epithelial Cell Line 
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  1. 1.
    Baldwin, A.S. Jr, K.P. Leclair, H. Singh, and P.A. Sharp. 1990. A large protein containing zinc finger domains binds to related sequence elements in the enhancers of the class I major histocompatibility complex and kappa immunoglobulin genes. Mol. Cell. Biol. 10:1406–1414.PubMedGoogle Scholar
  2. 2.
    Baldwin, A.S., Jr., and P.A. Sharp. 1988. Two transcription factors, NF-kB and H2TF1, interact with a single regulatory sequence in the class I major histocompatibility complex promoter. Proc. Natl. Acad. Sci. USA. 85: 723–727.PubMedCrossRefGoogle Scholar
  3. 3.
    Baldwin, A.S., Jr., and P.A. Sharp. 1987. Binding of a nuclear factor to a regulatory sequence in the promoter of the mouse H-2K° class I major histocompatibility gene. Mol. Cell. Biol. 7:305–313.PubMedGoogle Scholar
  4. 4.
    Bohnlein, E., J.W. Lowenthal, M. Siekevitz, D.W. Ballard, B.R. Franza, and W.C. Greene. 1988. The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV. Cell 53:827–836.PubMedCrossRefGoogle Scholar
  5. 5.
    Borras, T., C.A. Peterson, and J. Piatigorsky. 1988. Evidence for positive and negative regulation in the promoter of the chicken δ1-crystallin gene. Develop. Biol. 127:209–219.PubMedCrossRefGoogle Scholar
  6. 6.
    Chepelinsky, A.B., C.R. King, P.S. Zelenka, and J. Piatigorsky. 1985. Lens-specific expression of the chloramphenicol acetyltransferase gene promoted by 5’ flanking sequences of the murine αA-crystallin gene in explanted chicken lens epithelia. Proc. Natl. Acad. Sci. USA. 82:2334–2338.PubMedCrossRefGoogle Scholar
  7. 7.
    Chepelinsky, A.B., B. Sommer, and J. Piatigorsky. 1987. Interaction between two different regulatory elements activates the murine aA-crystallin gene promoter in explanted lens epithelia. Mol. Cell. Biol. 7:1807–1814.PubMedGoogle Scholar
  8. 8.
    Clark, L, R._M. Pollock, and R. T. Hay. 1988. Identification and purification of EBP1: a HeLa cell protein that binds to a region overlapping the ‘core’ of the SV40 enhancer. Genes Develop. 2:991–1002.PubMedCrossRefGoogle Scholar
  9. 9.
    Earle, W.R., E.L. Schilling, T.H. Stark, N.P. Straus, M.F. Brown, and E. Shelton. 1943. Production of malignancy in vitro. IV. The mouse fibroblast cultures and changes seen in the living cells. J. Natl. Cancer Inst. 4:165–212.Google Scholar
  10. 10.
    Fan, C-M, and T. Maniatis. 1990. A DNA-binding protein containing two widely separated zinc finger motifs that recognize the same DNA sequence. Genes & Develop. 4:29–42.CrossRefGoogle Scholar
  11. 11.
    Gerster, T., P. Matthias, M. Thali, J. Jiricny, and W. Schaffner. 1987. Cell type-specificity elements of the immunoglobulin heavy chain gene enhancer. EMBO J. 6:1323–1330.PubMedGoogle Scholar
  12. 12.
    Gorman, CM., G.T. Merlino, M.C. Williingham, I. Pastan, and B.H. Howard. 1982. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc. Natl. Acad. Sci. USA. 79:6777–6781.PubMedCrossRefGoogle Scholar
  13. 13.
    Goto, K., T.S. Okada, and H. Kondoh. 1990. Functional cooperation of lens-specific and nonspecific elements in the δ1-crystallin enhancer. Mol. Cell Biol.10:958–964.PubMedGoogle Scholar
  14. 14.
    Graham, F.L., and A.J. Van der Eb. 1973. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 52:456–467.PubMedCrossRefGoogle Scholar
  15. 15a.
    Hyman, R., P. Ralph, and S. Sarkar. 1972. Cell specific antigens and immune-globulin synthesis of murine myeloma cells and their variants. J. Natl. Cancer Inst. 48:173–184.PubMedGoogle Scholar
  16. 15b.
    Jaworski, C.J., A.B. Chepelinsky, and J. Piatigorsky 1991. The αA-crystallin gene: Conserved features of the 5’-flanking regions in human, mouse, and chicken, J. Mol. Evol. 33:495–505.PubMedCrossRefGoogle Scholar
  17. 16.
    Klement, J.F., E.F. Wawrousek, and J. Piatigorsky. 1989. Tissue-specific expression of the chicken αA-crystallin gene in cultured lens epithelia and transgenic mice. J. Biol. Chem. 264:19837–19844.PubMedGoogle Scholar
  18. 17.
    Lenardo, M.J., and D. Baltimore. 1989. NF-kB: A pleiotropic mediator of inducible and tissue-specific gene control. Cell. 58:227–229.PubMedCrossRefGoogle Scholar
  19. 18a.
    Matsuo, I., M. Kitamura, K. Okazaki, and K. Yasuda. 1991. Binding of a factor to an enhancer element responsible for the tissue-specific expression of the chicken αA-crystallin gene. Develop. 113:539–550.Google Scholar
  20. 18b.
    Maekawa, T., H. Sakura, T. Sudo, and S. Ishii. 1989. Putative metal finger structure of the human immunodeficiency virus type 1 enhancerbinding protein HIV-EPI. J. Biol. Chem. 246:14591–14593.Google Scholar
  21. 19.
    Miksicek, R., A. Heber, W. Schmid, U. Danesch, G. Possechert, M. Beato, and G Schutz. 1986. Glucocorticoid responsiveness of the transcriptional enhancer of moloney murine sarcoma virus. Cell 46:283–290.PubMedCrossRefGoogle Scholar
  22. 20.
    Nakamura, T., D.M. Donovan, K. Hamada, CM. Sax, B. Norman, J.R. Flanagan, K. Ozato, H. Westphal, and J. Piatigorsky. 1990. Regulation of the mouse αA-crystallin gene: Isolation of a cDNA encoding a protein that binds to a cis sequence motif shared with MHC class I and other genes. Mol. Cell. Biol. 10:3700–3708.PubMedGoogle Scholar
  23. 21.
    Neumann, J.R., C.A. Morency, and K.O. Russian. 1987. A novel rapid assay for chloramphenicol acetyltransferase gene expression. BioTech. 5:444–447.Google Scholar
  24. 22.
    Nielsen, D.A., J. Chou, A. J. Mackrell, M.J. Casadaban, and D.F. Steiner. 1983. Expression of a preproinsulin-β-galactosidase gene fusion in mammalian cells. Proc. Natl. Acad. Sci. USA. 80:5198–5202.PubMedCrossRefGoogle Scholar
  25. 23.
    Overbeek, P.A., A.B. Chepelinsky, J.S. Khillan, and J. Piatigorsky. 1985. Lens-specific expression and developmental regulation of the bacterial chloramphenicol acetyltrans-ferase gene driven by the murine αA-crystallin promoter in transgenic mice. Proc. Natl. Acad. USA. 82:7815–7819.CrossRefGoogle Scholar
  26. 24.
    Piatigorsky, J. 1989. Lens crystallins and their genes: diversity and tissue-specific expression. FASEB J. 3:1933–1940.PubMedGoogle Scholar
  27. 25.
    Sambrook, J., E.F. Fritsch, T. Maniatis. 1989. Transfection using DEAE-dextran: Protocol I. p. 16.42–16.44. In Molecular Cloning. A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.Google Scholar
  28. 26.
    Sax, CM., F.X. Farrell, Z.E. Zehner, and J. Piatigorsky. 1990. Regulation of vimentin gene expression in the ocular lens. Develop. Biol. 139:56–64.PubMedCrossRefGoogle Scholar
  29. 27.
    Sommer, B., A.B. Chepelinsky, and J. Piatigorsky. 1988. Binding of nuclear proteins to promote elements of the mouse αA-crystallin gene. J. Biol. Chem. 263:15666–15672.PubMedGoogle Scholar
  30. 28.
    Wawrousek, E.F., A.B. Chepelinsky, J.B. McDermott, and J. Piatigorsky. 1990. Regulation of the murine αA-crystallin promoter in transgenic mice. Develop. Biol. 137:68–76.PubMedCrossRefGoogle Scholar
  31. 29.
    Wirth, T. and D. Baltimore. 1988. Nuclear factor NF-KB can interact functionally with its cognate binding site to provide lymphoid-specific promoter function. EMBO J. 7:3109–3113.PubMedGoogle Scholar
  32. 30.
    Wistow, G.J., and J. Piatigorsky. 1988. Lens crystallins: The evolution and expression of proteins for a highly specialized tissue. Ann. Rev. Biochem. 57:479–504.PubMedCrossRefGoogle Scholar
  33. 31.
    Yamada, T., T. Nakamura, H. Westphal, and P. Russell. 1990. Synthesis of α-crystallin by a cell line derived from the lens of a transgenic animal. Curr. Eye Res. 9:31–37.PubMedGoogle Scholar
  34. 32.
    Yano, O., J. Kanellopoulos, M. Kieran, O. Le Bail, A. Isreal, and P. Kourilsky. 1987. Purification of KBF1, a common factor binding to both H-2 and β2-microglobulin enhancers. EMBO J. 6:3317–3324.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1992

Authors and Affiliations

  • Christina M. Sax
    • 1
  • John F. Klement
    • 1
  • Joram Piatigorsky
    • 1
  1. 1.Laboratory of Molecular and Developmental BiologyNational Eye Institute National Institutes of HealthBethesda

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