Expression and Chromatin Structure of the Alpha-Fetoprotein and Albumin Genes During Normal Development and Neoplasia

  • Jean-Louis Nahon
  • José M. Sala-Trepat
Part of the NATO ASI Series book series (NSSA, volume 101)


It is generally accepted that embryonic development and cell specialization is achieved via the sequential and selective expression of many genes. However, our knowledge concerning the molecular mechanisms responsible for changes in gene expression during developmental processes is still very limited. Within the last 10 years numerous investigations have aimed to elucidate the regulatory mechanisms that underlie the expression of specific genes associated with the formation of a particular cell type. Most of these studies have made use of terminally differentiated tissues or cells in culture, which in some cases can respond to environmental factors such as hormones (for reviews see references 1 and 2). At the level of cell culture, perhaps myogenesis and erythroid differentiation have received the greatest attention. Recently the use of teratomas has allowed analysis of the expression of individual, identified genes during early embryogenesis (3).


Chromatin Structure Adult Liver Adult Kidney Hypersensitive Site Albumin Gene 
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  1. 1.
    AHMAD, F., SCHULTZ, J., RUSSEL, T.R., and WERNER, R., eds. (1978). “Differentiation and Development,” Miami Winter Symposia, Vol. 15. Academic Press, New York.Google Scholar
  2. 2.
    BUCKINGHAM, M.E., ed. (1981). “Development and Differ- entiation.” CRC Press, Boca Roton, Florida.Google Scholar
  3. 3.
    SILVER, L.M., MARTIN, G.R., and STRICKLAND, S., eds. (1983). “Teratocarcinoma Stem Cells,” Cold Spring Harbor Conferences on Cell Proliferation, Vol. 10. Cold Spring Harbor Laboratory, New York.Google Scholar
  4. 4.
    DZIADEK, M. and ADAMSON, E. (1978). Localization and synthesis of alphafetoprotein in post implantation mouse embryos. J. Embryol. Exp. Morph. 43, 289–313.Google Scholar
  5. 5.
    PETERS, T., Jr. (1975). In: “The Plasma Proteins,” Vol. 1 (F.W. Putman, ed.) pp. 1317181. Academic Press, New York.Google Scholar
  6. 6.
    RUOSLAHTI, E. and SEPPALA, M. (1979). a-Fetoprotein in cancer and fetal development. Adv. Cancer Res. 29, 275346.Google Scholar
  7. 7.
    ABELEV, G.I. (1971). Alpha-fetoprotein in oncogenesis and its association with malignant tumors. Adv. Cancer Res. 14, 295–358.Google Scholar
  8. 8.
    GITLIN, D. and BOESMAN, M. (1967). Sites of serum a- fetoprotein synthesis in the human and in the rat. J. Clin. Invest. 46, 1010–1016.Google Scholar
  9. 9.
    GITLIN, D. and PERRICELLI, A. (1970). Synthesis of serum albumin, prealbumin, a-fetoprotein, la-antitrypsin, and transferrin by the human yolk sac. Nature 228, 995–997.PubMedCrossRefGoogle Scholar
  10. 10.
    DE NECHAUD, B. and URIEL, J. (1971). Antigenes cellulaires transitoires du foie de rat. I. Secretion et synthese des proteines seriques foetospecifiques au cours du developpement et de la regeneration hepatiques. Int. J. Cancer 8, 71–80.Google Scholar
  11. 11.
    VAN FURTH, R. and ADINOLFI, M. (1969). In vitro synthesis of the fetal al-globulin in man. Nature 222, 1296–1299.PubMedCrossRefGoogle Scholar
  12. 12.
    GITLIN, D. and GITLIN, J.D. (1975). In: “The Plasma Proteins,” Vol. 2 (F.W. Putnam, ed.) pp. 2T4–237. Academic Press, New York.Google Scholar
  13. 13.
    GITLIN, D. and KITZES, J. (1967). Synthesis of serum albumin, embryo specific a-globulin and conalbumin by the chick yolk sac. Biochim. Biophys. Acta 147, 334–340.Google Scholar
  14. 14.
    SELLEM, C., FRAIN, M., ERDOS, T., and SALA-TREPAT, J.M. (1984). Differential expression of albumin and a-fetoprotein genes in fetal tissues of mouse and rat. Dev. Biol. 102, 51–60.Google Scholar
  15. 15.
    BELANGER, L., HAMEL, D., LACHANCE, L., DUFOUR, D., TREMBLAY, M., and GAGNON, P.M. (1975). Hormonal regulation of al-fetoprotein. Nature 256, 657–659.PubMedCrossRefGoogle Scholar
  16. 16.
    SELL, S., BECKER, F., LEFFERT, H., and WATABE, H. (1976). Expression of an oncodevelopmental gene product (a-fetoprotein) during fetal development and adult oncogenesis. Cancer Res. 36, 4239–4249.PubMedGoogle Scholar
  17. 17.
    WATABE, H. (1971). Early appearance of embryonic a-globulin in rat serum during carcinogenesis with 4-dimethylamino azobenzene. Cancer Res. 31, 1192–1194.PubMedGoogle Scholar
  18. 18.
    SELL, S., SALA-TREPAT, J.M., SARGENT, T., THOMAS, K., NAHON, J.L., GOODMAN, T.A., and BONNER, J. (1980). Molecular mechanisms of control of albumin and alpha-fetoprotein production: a system to study the early effects of chemical hepatocarcinogens. Cell Biol. Intern. Rep. 4, 235–254.Google Scholar
  19. 19.
    ABELEV, G.I. (1974). a-Fetoprotein as a marker of embryo-specific differentiations in normal and tumor tissue. Transplant. Rev. 20, 3–37.Google Scholar
  20. 20.
    SELL, S. and MORRIS, H.P. (1974). Relationship of rat al–fetoprotein to growth rate and chromosome composition of Morris hepatomas. Cancer Res. 34, 1413–1417.PubMedGoogle Scholar
  21. 21.
    SCHREIBER, G., ROTERMUND, H.M., MAENO, H., WEIGAND, K., and LESHS, R. (1969). The proportion of the incorporation of leucine into albumin to that into total protein in rat liver and hepatoma Morris 5123TC. Eur. J. Biochem. 10, 355–361.Google Scholar
  22. 22.
    TSE, T.P.H., MORRIS, H.P., and TAYLOR, J.M. (1978). Molecular basis of reduced albumin synthesis in Morris Hepatoma 7777. Biochemistry 17, 21121–2128.CrossRefGoogle Scholar
  23. 23.
    SELL, S., THOMAS, K., MICHAELSON, M., and BONNER, J. (1979). Control of protein expression in rat liver and in hepatocellular carcinomas. Biochim. 173–178.Google Scholar
  24. 24.
    RUOSLAHTI, E. and ENGVALL, E. (1976). Immunological cross-reaction between alpha-fetoprotein and albumin. Proc. Natl. Acad. Sci. USA 73, 4641–4644.Google Scholar
  25. 25.
    RUOSLAHTI, E. and TERRY, W.D. (1976). Alpha-foetoprotein and serum albumin show sequence homology. Nature 260, 804–805.PubMedCrossRefGoogle Scholar
  26. 26.
    LIAO, W.S Amino acid albumin at 8046–8049.Google Scholar
  27. 27.
    JAGODZINSKI, L., SARGENT, T.D., YANG, M., GLACKIN, C., and BONNER, J. (1981). Sequence homology between RNAs encoding rat a-fetoprotein and rat serum albumin. Proc. Natl. Acad. Sci. USA 78, 3521–3525.Google Scholar
  28. 28.
    MORINAGA, T., SAKAI, M., WEGMANN, T.G., and TAMAOKI, T. (1983). Primary structures of human a-fetoprotein and its mRNA. Proc. Natl. Acad. Sci. USA 80, 4604–4608.Google Scholar
  29. 29.
    SARGENT, T., JAGODZINSKI, L., YANG, M., and BONNER, J. (1981). Fine structure and evolution of the rat serum albumin gene. Mol. Cell. Biol. 1, 871–883.Google Scholar
  30. 30.
    KIOUSSIS, D., EIFERMAN, F., VAN DE RIJN, P., GORIN, M.B., INGRAM, R.S., and TILGHMAN, S.H. (1981). The evolution of a-fetoprotein and albumin. II. The structures of the afetoprotein and albumin genes in the mouse. J. Biol. Chem. 256, 1960–1967.Google Scholar
  31. 31.
    ALEXANDER, F., YOUNG, P.R., and TILGHMAN, S.H. (1984). Evolution of the albumin-a-fetoprotein ancestral gene from the amplification of a 27 nucleotide sequence. J. Mol. Biol. 173, 159–176.Google Scholar
  32. 32.
    INGRAM, R.S., SCOTT, R.W., and TILGHMAN, S.M. (1981). aFetoprotein and albumin genes are in tandem in the mouse genome. Proc. Natl. Acad. Sci. USA 78, 4694–4698.Google Scholar
  33. 33.
    GROUDINE, M. and WEINTRAUB, H. (1981). Activation of globin genes during chicken development. Cell 24, 353–401.CrossRefGoogle Scholar
  34. 34.
    MANIATIS, T., FRISTSCH, E.F., LAUER, J., and LAWN, R.M. (1980). The molecular genetics of human hemoglobins. Ann. Rev. Genet. 14, 145–178.Google Scholar
  35. 35.
    INNIS, M.A. and MILLER, D. (1977). Quantitation of rat afetoprotein messenger RNA with a complementary DNA probe. J. Biol. Chem. 252, 8469–8475.Google Scholar
  36. 36.
    SALA-TREPAT, J.M., DEVER, J., SARGENT, T.D., THOMAS, K., SELL, S., and BONNER, J. (1979). Changes in expression of albumin and a-fetoprotein genes during rat liver development and neoplasia. Biochemistry 18, 2167–2178.CrossRefGoogle Scholar
  37. 37.
    MIURA, K., LAW, S.W., NISHI, S., and TAMAOKI, T. (1979). Isolation of a-fetoprotein messenger RNA from mouse yolk sac. J. Biol. Chem. 254, 5515–5521.Google Scholar
  38. 38.
    BROWN, R.D. and PAPACONSTANTINOU, J. (1979). Mouse albumin mRNA in liver and a hepatoma cell line. J. Biol. Chem. 254, 5177–5183.Google Scholar
  39. 39.
    SALA-TREPAT, J.M., SARGENT, T.D., SELL, S., and BONNER, J. (1979). a-Fetoprotein and albumin genes of rats: no evi-dence for amplification-deletion or rearrangement in rat liver carcinogenesis. Proc. Natl. Acad. Sci. USA 76, 695–699.Google Scholar
  40. 40.
    SARGENT, T.D., WU, J.R., SALA-TREPAT, J.M., WALLACE, R.B., REYES, A.A., and BONNER, J. (1979). The rat serum albumin gene: analysis of cloned sequences. Proc. Natl. Acad. Sci. USA 18, 3256–3260.Google Scholar
  41. 41.
    TILGHMAN,S.M., KIOUSSIS, D., GORIN, M.B., GARCIA RUIZ,J.P., and INGRAM, R.S. (1979). The presence of intervening sequences in the a-fetoprotein gene of the mouse. J. Biol.Chem. 254Google Scholar
  42. 42.
    LAW, S., TAMAOKI, T., KREUZALER, M., and DUGAICZYK, A. (1980). Molecular cloning of DNA complementary to a mouse a-fetoprotein mRNA sequence. Gene 10, 53–61.PubMedCrossRefGoogle Scholar
  43. 43.
    GAL, A., NAHON, J.L., LUCOTTE, G., and SALA-TREPAT, J.M. (1984). Structural variants of the a-fetoprotein gene in different inbred strains of rat. Mol. Gen. Genet. 195, 153–158.Google Scholar
  44. 44.
    DUGAICZYK, A., LAW, S.W., and DENNISON, D.E. (1982). Nucleotide sequence and the encoded amino-acids of human serum albumin mRNA. Proc. Natl. Acad. Sci. USA 79, 71–75.Google Scholar
  45. 45.
    FRAIN, M. (1984). Structure et expression des genes codant pour deux proteines marqueurs de la differenciation hepatique chez l’homme: l’albumine et l’alpha-foetoproteine. These d’Etat, University of Paris.Google Scholar
  46. 46.
    LIAO, W.S.L., CONN, A.R., and TAYLOR, J.M. (1980). Changes in rat al-fetoprotein and albumin mRNA levels during fetal and neonatal development. J. Biol. Chem. 255, 10036–10039.Google Scholar
  47. 47.
    CASSIO, D., WEISS, M.C., OTT, M.O., SALA-TREPAT, J.M., FRIES, J., and ERDOS, T. (1981). Expression of the albumin gene in rat hepatoma cells and their dedifferentiated variants. Cell 27, 351–358.Google Scholar
  48. 48.
    NAHON, J.L., GAL, A., FRAIN, M., SELL, S., and SALA-TREPAT, J.M. (1982). No evidence for post-transcriptional control of albumin and a-fetoprotein gene expression in developing rat liver and neoplasia. Nucleic Acids Res. 10, 1895–1911.PubMedCrossRefGoogle Scholar
  49. 49.
    BELANGER, L., FRAIN, M., BARIL, P., GINGRAS, M.C., BARTKOWIAK, J., and SALA-TREPAT, J.M. (1981). Glucocorticoid supression of a fetoprotein synthesis in developing rat liver. Evidence Tor selective gene repression at the transcriptional level. Biochemistry 20, 6665–6671.Google Scholar
  50. 50.
    TILGHMAN, S.H. and BELAYEW, A. (1982). Transcriptional control of the murine albumin/a-fetoprotein locus during development. Proc. Natl. Acad. Sci. USA 79, 5254–5257.Google Scholar
  51. 51.
    GUERTIN, M., BARIL, P., BARTKOWIAK, J., ANDERSON, A., and BELANGER, L. (1983). Rapid supression of al-fetoprotein gene transcription by dexamethasone in developing rat liver. Biochemistry22, 4296–4302.PubMedCrossRefGoogle Scholar
  52. 52.
    ANDREWS, G.K., DZIADEK, M., and TAMAOKI, T. (1982). Expression and methylation of the mouse a-fetoprotein gene in embryonic, adult, and neoplastic tissues. J. Biol. Chem. 257, 5148–5153.Google Scholar
  53. 53.
    RAZIN, A. and RIGGS, A.D. (1980). DNA methylation and gene function. Science 210, 604–610.PubMedCrossRefGoogle Scholar
  54. 54.
    DOERFLER, W. (1983). DNA methylation and gene activity. Ann. Rev. Biochem. 52, 93–124.Google Scholar
  55. 55.
    VEDEL, M., GOMEZ-GARCIA, M., SALA, M., and SALA-TREPAT, J.M. (1983). Changes in methylation pattern of albumin and a-fetoprotein genes in developing rat liver and neoplasia. Nucleic Acids Res. 11, 4335–4354.Google Scholar
  56. 56.
    KUNNATH, L. and LOCKER, J. (1983). Developmental changes in the methylation of the rat albumin and a-fetoprotein genes. EMBO J. 2, 317–324.PubMedGoogle Scholar
  57. 57.
    OTT, M.O., SPERLING, L., CASSIO, D., LEVILLIERS, J., SALATREPAT, J.M., and WEISS, M.C. (1982). Undermethylation at the 5’-end of the albumin gene is necessary but not sufficient for albumin production by rat hepatoma cells in culture. Cell 30, 825–833.PubMedCrossRefGoogle Scholar
  58. 58.
    FELSENFELD, G. (1978). Chromatin. Nature 271, 115–122.CrossRefGoogle Scholar
  59. 59.
    MATHIS, D., OUDET, P., and CHAMBON, P. (1980). Structure of transcribing chromatin. Progr. Nucleic Acid Res. Mol. Biol. 24, 1–54.Google Scholar
  60. 60.
    WEINTRAUB, H. and GROUDINE, M. (1976). Chromosomal subunits in active genes have an altered conformation: globin genes are digested by deoxyribonuclease I in red blood cell nuclei but not in fibroblast nuclei. Science 193, 848–856.PubMedCrossRefGoogle Scholar
  61. 61.
    WEISBROD, S. (1982). Active chromatin. Nature 297, 289–295.PubMedCrossRefGoogle Scholar
  62. 62.
    WU, C. (1980). The 5’ end of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature 286, 854–860.PubMedCrossRefGoogle Scholar
  63. 63.
    ELGIN, S.C.R. (1981). DNase I-hypersensitive sites on chromatin. Cell 27, 413–415.PubMedCrossRefGoogle Scholar
  64. 64.
    NAHON, J.L., GAL, A., ERDOS, T., and SALA-TREPAT, J.M. (1984). Differential DNase I sensitivity of the albumin and a-fetoprotein genes in chromatin from rat tissues and cell lines. Proc. Natl. Acad. Sci. USA 81, 5031–5035.Google Scholar
  65. 65.
    NAHON, J.L. and SALA-TREPAT, J.M. (1984). Tissue-specific DNase I hypersensitive sites in rat chromatin are present upstream from the 5’ ends of the albumin and a-fetoprotein genes. J. Cell Biol. 99, 139a.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Jean-Louis Nahon
    • 1
  • José M. Sala-Trepat
    • 1
  1. 1.Laboratoire d’Enzymologie du C.N.R.S.Gif-sur-YvetteFrance

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