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Genomic Imprinting in Mammals

Abstract

A review of the data on the mechanisms and effects of genomic imprinting, an epigenetic phenomenon regulating the development in placentate mammals, is presented. In contrast to the majority of gene loci with biallelic expression, the expression of imprinted loci is monoallelic. In humans and mice, more than 30 imprinted loci have been identified, in which maternal or paternal alleles may either be expressed or be found in a repressed state during ontogeny. Imprinting is established during gametogenesis, and the repression of an allele of the imprinted locus is determined by methylation of the key regulatory element of this allele. Both the maternal and paternal chromosome sets are required for normal development in mammals. This is why parthenogenesis and androgenesis in these animals are impossible in nature. As a result of differential gene expression of many imprinted loci, the balance of gene activity is established, which is necessary for normal proliferation and differentiation of various cell clones in embryogenesis. Many human developmental abnormalities and syndromes are determined by defective genomic imprinting. In particular, the loss of imprints, which is followed by the occurrence of biallelic expression of some imprinted loci, may cause malignant tumors.

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REFERENCES

  1. Savory, T.H., The Mule, Sci. Am., 1970, vol.223, no. 6, pp. 102-109.

    Google Scholar 

  2. Surani, M.A.H. and Barton, S.C., Development of Gynogenetic Eggs in the Mouse: Implications for Parthenogenetic Embryos, Science, 1983, vol. 222, pp. 1034-1036.

    Google Scholar 

  3. Barton, S.C., Surani, M.A.H., and Norris, M.L., Role of Paternal and Maternal Genomes in Mouse Development, Nature, 1984, vol. 311, pp. 374-376.

    Google Scholar 

  4. Surani, M.A.H., Barton, S.C., and Norris, M.L., Development of Reconstituted Mouse Eggs Suggests Imprinting of the Genome during Gametogenesis, Nature, 1984, vol. 308, pp. 548-550.

    Google Scholar 

  5. Surani, M.A.H., Barton, S.C., and Norris, M.L., Nuclear Transplantation in the Mouse: Heritable Differences between Parental Genomes after Activation of the Embryonic Genome, Cell (Cambridge, Mass.), 1986, vol. 45, pp. 127-136.

    Google Scholar 

  6. McGrath, J. and Solter, D., Nuclear Transplantation in Mouse Embryos, J. Exp. Zool., 1983, vol. 228, pp. 355-362.

    Google Scholar 

  7. McGrath, J. and Solter, D., Completion of Mouse Embryogenesis Requires Both the Maternal and Paternal Genomes, Cell (Cambridge, Mass.), 1984, vol. 37, pp. 179-183.

    Google Scholar 

  8. Chandra, H.S. and Brown, S.W., Chromosome Imprinting and the Mammalian X Chromosome, Nature, 1975, vol. 253, pp. 165-168.

    Google Scholar 

  9. Baranov, V.S., Chromosome Imprinting and Interchromosomal Interactions in the Early Development of Mammals, Usp. Sovrem. Biol., 1988, vol. 105, no. 3, pp. 393-405.

    Google Scholar 

  10. Barlow, D.P., Competition-A Common Motif for the Imprinting, EMBO J., 1997, vol. 16, pp. 6899-6905.

    Google Scholar 

  11. Falls, J.G., Pulford, D.J., Wylie, A.A., and Jirtle, R.L., Genomic Imprinting: Implications for Human Disease, Am. J. Pathol., 1999, vol. 154, pp. 635-647.

    Google Scholar 

  12. Solter, D., Imprinting, Int. J. Dev. Biol., 1998, vol. 42, pp. 951-954.

    Google Scholar 

  13. Murphy, S.K. and Jirtle, R.L., Imprinted Genes as Potential Genetic and Epigenetic Toxicologic Targets, Environ. Health Perspect., vol. 108, suppl. 1, pp. 5-11.

  14. Vielle-Calzada, J.-P., Thomas, J., Spillane, C., et al., Maintenance of Genomic Imprinting at the Arabidopsis medea Locus Requires Zygotic DDM1 Activity, Genes Dev., 1999, vol. 13, pp. 2971-2982.

    Google Scholar 

  15. Mora-Garcia, S. and Goodrich, J., Genomic Imprinting: Seeds of Conflict, Curr. Biol., 2000, vol. 10, pp. 71-74.

    Google Scholar 

  16. Searle, A.G. and Beechey, C.V., Complementation Studies with Mouse Translocations, Cytogenet. Cell Genet., 1978, vol. 20, pp. 282-303.

    Google Scholar 

  17. Searle, A.G. and Beechey, C.V., Genome Imprinting Phenomena on Mouse Chromosome 7, Genet. Res., 1990, vol. 56, pp. 237-244.

    Google Scholar 

  18. Cattanach, B.M., Non-Disjunction Tests with Robertsonian Translocations, Mouse Newslett., 1982, no. 66, pp. 62-63.

    Google Scholar 

  19. Cattanach, B.M., Parental Origin Effects in Mice, J. Embryol. Exp. Morph. Suppl., 1986, vol. 97, pp. 137-150.

    Google Scholar 

  20. Cattanach, B.M. and Kirk, M., Differential Activity of Maternally and Paternally Derived Chromosome Regions in Mice, Nature, 1985, vol. 315, pp. 496-498.

    Google Scholar 

  21. Cattanach, B.M., Beechey, C.V., Evans, E.P., and Burtenshaw, M., Further Localization of the Distal Chromosome 2 Imprinting Region, Mouse Genome, 1991, vol. 89, p. 255.

    Google Scholar 

  22. Beechey, C.V. and Cattanach, B.M., Genetic Imprinting Map, Mouse Genome, 1996, vol. 94, pp. 96-99.

    Google Scholar 

  23. Morison, I.M. and Reeve, A.E., A Catalogue of Imprinted Genes and Parent-of-Origin Effects in Humans and Animals, Hum. Mol. Genet., 1998, vol. 7, pp. 1599-1609.

    Google Scholar 

  24. DeChiara, T.M., Robertson, E.J., and Efstratiadis, A., Parental Imprinting of the Mouse Insulin-Like Growth Factor-II Gene, Cell (Cambridge, Mass.), 1991, vol. 64, pp. 849-859.

    Google Scholar 

  25. Barlow, D.P., Stöger, R., Herrmann, B.G., et al., The Mouse Insulin-Like Growth Factor Type-2 Receptor Is Imprinted and Closely Linked to the Tme Locus, Nature, 1991, vol. 349, pp. 84-87.

    Google Scholar 

  26. Bartolomei, M.S., Zemel, S., and Tilghman, S.M., Parental Imprinting of the Mouse H19 Gene, Nature, 1991, vol. 351, pp. 153-155.

    Google Scholar 

  27. Wevrick, R. and Francke, U., An Imprinted Mouse Transcript Homologous to the Human Imprinted in Prader-Willi Syndrome ( IPW ) Gene, Hum. Mol. Genet., 1997, vol. 6, pp. 325-332.

    Google Scholar 

  28. Brannan, C.I., Dees, E.C., Ingram, R.S., and Tilghman, S.M., The Product of the H19 Gene May Function as an RNA, Mol. Cell. Biol., 1990, vol. 10, pp. 28-36.

    Google Scholar 

  29. Guillemot, F., Caspary, T., Tilghman, S.M., et al., Genomic Imprinting of Mash-2, a Mouse Gene Required for Trophoblast Development, Nat. Genet., 1995, vol. 9, pp. 235-241.

    Google Scholar 

  30. Lerchner, W. and Barlow, D.P., Paternal Repression of the Imprinted Mouse Igf2r Locus Occurs during Implantation and Is Stable in All Tissues of the Postimplantation Mouse Embryo, Mech. Dev., 1997, vol. 61, pp. 141-149.

    Google Scholar 

  31. Vu, T.H. and Hoffman, A.R., Promoter-Specific Imprinting of the Human Insulin-like Growth Factor-II Gene, Nature, 1994, vol. 371, pp. 714-717.

    Google Scholar 

  32. Ekstrom, T.J., Cui, H., Li, X., and Ohlsson, R., Promoter-Specific IGF2 Imprinting Status and Its Plasticity during Human Liver Development, Development (Cambridge, UK), 1995, vol. 121, pp. 309-316.

    Google Scholar 

  33. Jinno, Y., Ikeda, Y., Yun, K., et al., Establishment of Functional Imprinting of the H19 Gene in Human Developing Placentae, Nat. Genet., 1995, vol. 10, pp. 318-324.

    Google Scholar 

  34. Giddings, S.J., King, C.D., Harman, K.W., et al., Allele Specific Inactivation of Insulin 1 and 2, in the Mouse Yolk Sack, Indicates Imprinting, Nat. Genet., 1994, vol. 6, pp. 310-313.

    Google Scholar 

  35. Lee, M.P., Hu, R., Johnson, L.A., and Feinberg, A.P., Human KvLQT1 Gene Shows Tissue-Specific Imprinting and Encompasses Beckwith-Wiedemann Syndrome Chromosomal Rearrangements, Nat. Genet., 1997, vol. 15, pp. 181-185.

    Google Scholar 

  36. Szabo, P.E. and Mann, J.R., Allele-Specific Expression and Total Expression Levels of Imprinted Genes during Early Mouse Development: Implications for Imprinting Mechanisms, Genes Dev., 1995, vol. 9, pp. 3097-3108.

    Google Scholar 

  37. Tremblay, R.D., Saam, J.R., Ingram, R.S., et al., A Paternal-Specific Methylation Imprint Marks the Alleles of the Mouse H19 Gene, Nat. Genet., 1995, vol. 9, pp. 407-413.

    Google Scholar 

  38. Bartolomei, M.S. and Tilghman, S.M., Genomic Imprinting in Mammals, Annu. Rev. Genet., 1997, vol. 31, pp. 493-525.

    Google Scholar 

  39. Kay, G.F., Barton, S.C., Surani, M.A., and Rastan, S., Imprinting and X Chromosome Counting Mechanisms Determine Xist Expression in Early Mouse Development, Cell (Cambridge, Mass.), 1994, vol. 77, pp. 639-650.

    Google Scholar 

  40. Brockdorff, N., Ashworth, A., Kay, G.F., et al., Conservation of Position and Exclusive Expression of Mouse Xist from the Inactive X Chromosome, Nature, 1991, vol. 351, pp. 329-331.

    Google Scholar 

  41. Brown, C.J., Ballabio, A., Rupert, J.L., et al., A Gene From the Region of the Human X-Chromosome Inactivation Center Is Expressed Exclusively from the Inactive X Chromosome, Nature, 1991, vol. 349, pp. 38-44.

    Google Scholar 

  42. Takagi, N. and Sasaki, M., Preferential Inactivation of the Paternally Derived X Chromosome in the Extraembryonic Membranes of the Mouse, Nature, 1975, vol. 256, pp. 640-642.

    Google Scholar 

  43. Goto, T., Wright, E., and Monk, M., Paternal X-Chromosome Inactivation in Human Trophoblastic Cells, Mol. Hum. Reprod., 1997, vol. 3, pp. 77-80.

    Google Scholar 

  44. Li, E., Bestor, T.H., and Jaenisch, R., Targeted Mutation of the DNA Methyltransferase Gene Results in Embryonic Lethality, Cell (Cambridge, Mass.), 1992, vol. 69, pp. 915-926.

    Google Scholar 

  45. Li, E., Beard, C., and Jaenisch, R., The Role for DNA Methylation in Genomic Imprinting, Nature, 1993, vol. 366, pp. 362-365.

    Google Scholar 

  46. Caspary, T., Cleary, M.A., Baker, C.C., et al., Multiple Mechanisms Regulate Imprinting of the Mouse Distal Chromosome 7 Gene Cluster, Mol. Cell. Biol., 1998, vol. 18, pp. 3466-3474.

    Google Scholar 

  47. Walsh, C.P. and Bestor, T.H., Cytosine Methylation and Mammalian Development, Genes Dev., 1999, vol. 13, pp. 26-34.

    Google Scholar 

  48. Feil, R. and Khosla, S., Genomic Imprinting in Mammals: An Interplay between Chromatin and DNA Methylation?, Trends Genet., 1999, vol. 15, pp. 431-435.

    Google Scholar 

  49. Monk, M., Boubelik, M., and Lehnert, S., Temporal and Regional Changes in DNA Methylation in the Embryonic, Extraembryonic, and Germ Cell Lineages during Mouse Embryo Development, Development (Cambridge, UK), 1987, vol. 99, pp. 371-382.

    Google Scholar 

  50. Howlett, S.K. and Reik, W., Methylation Levels of Maternal and Paternal Genomes during Preimplantation Development, Development (Cambridge, UK), 1991, vol. 113, pp. 119-127.

    Google Scholar 

  51. Kafri, T., Ariel, M., Brandeis, M., et al., Developmental Pattern of Gene-Specific DNA Methylation in the Mouse Embryo and Germ Line, Genes Dev., 1992, vol. 6, pp. 705-714.

    Google Scholar 

  52. Jaenisch, R., DNA Methylation and Imprinting: Why Bother?, Trends Genet., 1997, vol. 13, pp. 323-329.

    Google Scholar 

  53. Surani, A., Imprinting and the Initiation of Gene Silencing in the Germ Line, Cell (Cambridge, Mass.), 1998, vol. 93, pp. 309-312.

    Google Scholar 

  54. Olek, A. and Walter, J., The Pre-Implantation Ontogeny of the H19 Methylation Imprint, Nat. Genet., 1997, vol. 17, pp. 275-276.

    Google Scholar 

  55. Mayer, W., Niveleau, A., Walter, J., et al., Demethylation of the Zygotic Paternal Genome, Nature, 2000, vol. 403, pp. 501-502.

    Google Scholar 

  56. Penkov, L.I., Platonov, E.S., Mironova, O.V., and Konyukhov, B.V., Effects of 5-Azacytidine on the Development of Parthenogenetic Mouse Embryos, Dev. Growth Diff., 1996, vol. 38, pp. 263-270.

    Google Scholar 

  57. Kato, Y., Rideout, W.M. III, Hilton, K., et al., Developmental Potential of Mouse Primordial Germ Cells, Development (Cambridge, UK), 1999, vol. 126, pp. 1823-1832.

    Google Scholar 

  58. Reik, W. and Walter, J., Imprinting Mechanisms in Mammals, Curr. Opin. Genet. Dev., 1998, vol. 8, pp. 154-164.

    Google Scholar 

  59. Kaufman, M.H., Early Mammalian Development: Parthenogenetic Studies, London: Cambridge Univ., 1983.

    Google Scholar 

  60. Dyban, A.P. and Noniashvili, E.M., Parthenogenesis in Mammals, Ontogenez, 1986, vol. 17, no. 4, pp. 368-388.

    Google Scholar 

  61. Kono, T., Obata, Y., Yoshimizu, T., et al., Epigenetic Modifications during Oocyte Growth Correlates with Extended Parthenogenetic Development in the Mouse, Nat. Genet., 1996, vol. 13, pp. 91-94.

    Google Scholar 

  62. Obata, Y., Kaneko-Ishino, T., Koide, T., et al., Disruption of Primary Imprinting during Oocyte Growth Leads to the Modified Expression of Imprinted Genes during Embryogenesis, Development (Cambridge, UK), 1998, vol. 125, pp. 1553-1560.

    Google Scholar 

  63. Coulier, F., Pontarotti, P., Roubin, R., et al., Of Worms and Men: An Evolutionary Perspective on the Fibroblast Growth Factor (FGF) and FGF Receptor Families, J. Mol. Evol., 1997, vol. 44, pp. 43-56.

    Google Scholar 

  64. Keresztes, M. and Boonstra, J., Import(ance) of Growth Factors in(to) The Nucleus, J. Cell Biol., 1999, vol. 145, pp. 421-424.

    Google Scholar 

  65. Penkov, L.I. and Platonov, E.S., The Effect of Fibroblast Growth Factors (FRF-2, FRF-4) on the Development of Parthenogenetic Mouse Embryos, Ontogenez, 1999, vol. 30, no. 6, pp. 448-452.

    Google Scholar 

  66. Platonov, E.S., Penkov, L.I., Kondrakhina, M.S., et al., Growth Factors Modulate the Effects of Genome Imprinting in Parthenogenetic Mouse Embryos, Tezisy dokladov II s''ezda VOGIS (Proc. II Meeting of VOGIS), St. Petersburg, 2000, vol. 2, p. 253.

    Google Scholar 

  67. Allen, N.D., Barton, S.C., Hilton, K., et al., A Functional Analysis of Imprinting in Parthenogenetic Embryonic Stem Cells, Development (Cambridge, UK), 1994, vol. 120, pp. 1473-1482.

    Google Scholar 

  68. McLaren, A., Mammalian Chimaeras, London: Cambridge Univ., 1976.

    Google Scholar 

  69. Konyukhov, B.V., Kupriyanov, S.D., and Isabekov, B.S., Use of Chimeric Transgenic Animals in Studying Gene Expression during Ontogeny, Usp. Sovrem. Genet., Moscow: Nauka, 1988, vol. 15, pp. 106-142.

    Google Scholar 

  70. Surani, M.A., Barton, S.C., and Kaufman, M.H., Development to Term of Chimaeras between Diploid Parthenogenetic and Fertilized Embryos, Nature, 1977, vol. 270, pp. 601-603.

    Google Scholar 

  71. Stevens, L.C., Totipotent Cells of Parthenogenetic Origin in a Chimaeric Mouse, Nature, 1978, vol. 276, pp. 266-267.

    Google Scholar 

  72. Stevens, L.C., Varnum, D.S., and Eicher, E.M., Viable Chimaeras Produced from Normal and Parthenogenetic Mouse Embryos, Nature, 1977, vol. 269, pp. 515-517.

    Google Scholar 

  73. Fundele, R., Norris, M.L., Barton, S.C., et al., Systematic Elimination of Parthenogenetic Cells in Mouse Chimaeras, Development (Cambridge, UK), 1989, vol. 106, pp. 20-35.

    Google Scholar 

  74. Fundele, R.H., Norris, M.L., Barton, S.C., et al., Temporal and Spatial Selection against Parthenogenetic Cells during Development of Fetal Chimeras, Development (Cambridge, UK), 1990, vol. 108, pp. 203-211.

    Google Scholar 

  75. Nagy, A., Sass, M., and Markkula, M., Systematic Non-Uniform Distribution of Parthenogenetic Cells in Adult Mouse Chimeras, Development (Cambridge, UK), 1989, vol. 106, pp. 321-324.

    Google Scholar 

  76. Isaev, D.A., Platonov, E.S., and Konyukhov, B.V., Distribution of Parthenogenetic Epidermal Melanoblast Clones in Chimeric C57BL/6(PG) BALB/c Mice, Ontogenez, 1997, vol. 28, no. 4, pp. 306-313.

    Google Scholar 

  77. Isaev, D.A., Mironova, O.V., Platonov, E.S., and Konyukhov, B.V., Analysis of Parthenogenetic Cell Clones in Chimeric C57BL/6 (PG) BALB/c Mice, Ontogenez, 1999, vol. 30, no. 1, pp. 64-70.

    Google Scholar 

  78. Paldi, A., Nagy, A., Markkula, M., et al., Postnatal Development of Parthenogenetic Fertilized Mouse Aggregation Chimeras, Development (Cambridge, UK), 1989, vol. 105, pp. 115-118.

    Google Scholar 

  79. Nagy, A., Paldi, A., Dezso, L., et al., Prenatal Fate of Parthenogenetic Cells in Mouse Aggregation Chimaeras, Development (Cambridge, UK), 1987, vol. 101, pp. 67-71.

    Google Scholar 

  80. Surani, M.A., Barton, S.C., Howlett, S.K., and Norris, M.L., Influence of Chromosomal Determinants on Development of Androgenetic and Parthenogenetic Cells, Development (Cambridge, UK), 1988, vol. 103, pp. 171-178.

    Google Scholar 

  81. Thomson, J.A. and Solter, D., The Developmental Fate of Androgenetic, Parthenogenetic, and Gynogenetic Cells in Chimeric Gastrulating Mouse Embryos, Genes Dev., 1988, vol. 2, pp. 1344-1351.

    Google Scholar 

  82. Barton, S.C., Ferguson-Smith, A.C., Fundele, R., and Surani, M.A., Influence of Paternally Imprinted Genes on Development, Development (Cambridge, UK), 1991, vol. 113, pp. 679-688.

    Google Scholar 

  83. Surani, M.A.H., Barton, S.C., and Norris, M.L., Influence of Parental Chromosomes on Spatial Specificity in Androgenetic Parthenogenetic Chimaeras in the Mouse, Nature, 1987, vol. 326, pp. 395-397.

    Google Scholar 

  84. Wolffe, A.P. and Matzke, M.A., Epigenetics: Regulation through Repression, Science, 1999, vol. 286, pp. 481-486.

    Google Scholar 

  85. Puzyrev, V.P. and Stepanov, V.A., Patologicheskaya anatomiya genoma cheloveka (Morbid Anatomy of the Human Genome), Novosibirsk: Nauka, 1997.

    Google Scholar 

  86. Rainier, S., Johnson, L.A., Dobry, C.J., et al., Relaxation of Imprinted Genes in Human Cancer, Nature, 1993, vol. 362, pp. 747-749.

    Google Scholar 

  87. Ogawa, O., Eccles, M.R., Szeto, J., et al., Relaxation of Insulin-like Growth Factor II Gene Imprinting Implicated in Wilms' Tumor, Nature, 1993, vol. 362, pp. 749-751.

    Google Scholar 

  88. Jirtle, R.L., Genomic Imprinting and Cancer, Exp. Cell Res., 1999, vol. 248, pp. 18-24.

    Google Scholar 

  89. Cui, H., Horon, I.L., Ohlsson, R., et al., Loss of Imprinting in Normal Tissue of Colorectal Cancer Patients with Microsatellite Instability, Nat. Med., 1998, vol. 4, pp. 1276-1280.

    Google Scholar 

  90. Morison, I.M. and Reeve, A.E., Insulin-Like Growth Factor 2 and Overgrowth: Molecular Biology and Clinical Implications, Mol. Med. Today, 1998, March, pp. 110-115.

  91. Tilghman, S.M., The Sins of the Fathers and Mothers: Genomic Imprinting in Mammalian Development, Cell (Cambridge, Mass.), 1999, vol. 96, pp. 185-193.

    Google Scholar 

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Konyukhov, B.V., Platonov, E.S. Genomic Imprinting in Mammals. Russian Journal of Genetics 37, 1–12 (2001). https://doi.org/10.1023/A:1009002106313

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Keywords

  • Gene Expression
  • Malignant Tumor
  • Gene Activity
  • Regulatory Element
  • Gene Locus