Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Physical linkage of two mammalian imprinted genes, H19 and insulin–like growth factor 2

Nature Genetics volume 2, pages 61–65 (1992)Cite this article

Abstract

Parental imprinting is a phenomenon in mammals whereby the maternal and paternal alleles of a gene are differentially expressed. Three murine genes have been shown to display this type of allele–specific expression. Two of them, insulin–like growth factor–2 (Igf–2) and H19, map to the distal end of mouse chromosome 7, but are imprinted in opposite directions. Pulsed–field gel electrophoresis and large–fragment DNA cloning were utilized to establish a physical map that includes H19 and Igf–2. Igf–2 lies ∼90 kilobases of DNA 5′ to H19, in the same transcriptional orientation. This physical proximity is conserved in humans, based on pulsed–field gel analysis. We conclude that H19 and Igf–2 constitute an imprinted domain.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. McGrath, J. & Solter, D. Inability of mouse blastomere nuclei transferred to enucleated zygotes to support development in vitro. Science 226, 1317–1319 (1984).

    Article  CAS  PubMed  Google Scholar 

  2. Surani, M.A.H., Barton, S.C. & Norris, M.L. Development of reconstituted mouse eggs suggest imprinting of the genome during gametogenesis. Nature 308, 548–550 (1984).

    Article  CAS  PubMed  Google Scholar 

  3. Barton, S.C., Surani, M.A.H. & Norris, M.L. Role of paternal and maternal genomes in mouse development. Nature 311, 374–376 (1984).

    Article  CAS  PubMed  Google Scholar 

  4. Cattanach, B.M. Non-disjunction tests with Robertsonian translocations. Mouse News Lett. 66, 62–63 (1982).

    Google Scholar 

  5. Cattanach, B.M. & Kirk, M. Differential activity of maternally and paternally derived chromosome regions in mice. Nature 315, 496–498 (1985).

    Article  CAS  PubMed  Google Scholar 

  6. Cattanach, B.M. Parental origin effects in mice. J. embrol. exp. Morph. Suppl. 97, 137–150 (1986).

    Google Scholar 

  7. Searle, A.G. & Beechey, C.V. Genome imprinting phenomena on mouse chromosome 7. Genet. Res. 56, 237–244 (1990).

    Article  CAS  PubMed  Google Scholar 

  8. Barlow, D.P., Stoger, R., Herrmann, B.G., Saito, K. & Schweifer, N. The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature 349, 84–87 (1991).

    Article  CAS  PubMed  Google Scholar 

  9. DeChiara, T.M., Robertson, E.J. & Efstratiadis, A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64, (1991).

    Article  CAS  PubMed  Google Scholar 

  10. Brannan, C.I., Dees, E.C., Ingram, R.S. & Tilghman, S.M. The product of the H19 gene may function as an RNA. Molec. Cell. Biol. 10, 28–36 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bartolomei, M.S., Zemel, S. & Tilghman, S.M. Parental imprinting of the mouse H19 gene. Nature 351, 153–155 (1991).

    Article  CAS  PubMed  Google Scholar 

  12. Pachnis, V., Brannan, C.I. & Tilghman, S.M. The structure and expression of a novel gene activated in early mouse embryogenesis. EMBO J. 7, 673–681 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Rossi, J.M. et al. Genomic analysis using a yeast artificial chromosome library with mouse DNA inserts. Proc. natn. Acad. Sci. U.S.A. 89, 2456–2460 (1992).

    Article  CAS  Google Scholar 

  14. Rotwein, P. & Hall, L.J. Evolution of Insulin-like Growth Factor II: Characterization of the Mouse IGF-II Gene and Identification of Two Pseudo-Exons. DNA Cell Biol. 9, 725–735 (1990).

    Article  CAS  PubMed  Google Scholar 

  15. Soares, M.B. et al. Rat insulin-like growth factor II gene: a single gene with two promoters expressing a multitranscript family. J. molec. Biol. 192, 737–752 (1986).

    Article  CAS  PubMed  Google Scholar 

  16. Bell, G.I., Gerhard, D.S., Fong, N.M., Sanchez-Pescador, R. & Rall, L.B. Isolation of the human insulin-like growth factor genes: insulin-like growth factor II and insulin genes are contiguous. Proc. natn. Acad. Sci. U.S.A. 82, 6450–6454 (1985).

    Article  CAS  Google Scholar 

  17. Riley, J. et al. A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones. Nucl. Acids Res. 18, 2887–90 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wentworth, B.M., Scharfer, I.M., Villa-Komaroff, L. & Chirgwin, J.M. Characterization of the two nonallelic genes encoding mouse preproinsulin. J. molec. Evol. 23, 305–312 (1986).

    Article  CAS  PubMed  Google Scholar 

  19. Glaser, T., Housman, D., Lewis, W.H., Gerhard, D. & Jones, C. A fine-structure deletion map of human chromosome 11p: analysis of J1 series hybrids. Somat. cell. Mol. Genet. 15, 477–501 (1989).

    Article  CAS  PubMed  Google Scholar 

  20. O'Malley, K.L. & Rotwein, P. Human tyrosine hydroxylase and insulin genes are contiguous on chromosome 11. Nucl. Acids Res. 16, 4437–4446 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Poirier, F. et al. The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo. Develop. 113, 1105–1114 (1991).

    CAS  Google Scholar 

  22. Lee, J.E., Pintar, J. & Efstratiadis, A. Pattern of the insulin-like growth factor II gene expression during early mouse embryogenesis. Develop. 110, 151–159 (1990).

    CAS  Google Scholar 

  23. Brunkow, M.E. & Tilghman, S.M. Ectopic expression of the H19 gene in mice causes prenatal lethality. Genes & Devl. 5, 1092–1101 (1991).

    Article  CAS  Google Scholar 

  24. Bartolomei, M.S. & Tilghman, S.M. Parental imprinting of mouse chromosome 7 Sem. develop. Biol. 3, 107–117 (1992).

    Google Scholar 

  25. Nickol, J.M. & Felsenfeld, G. Bidirectional control of the chicken β- and ɛ-globin genes by a shared enhancer. Proc. natn. Acad. Sci. U.S.A. 85, 2548–2552 (1988).

    Article  CAS  Google Scholar 

  26. Choi, O.-R.B. & Engel, J.D. Developmental regulation of β-globin switching. Cell 55, 17–26 (1988).

    Article  CAS  PubMed  Google Scholar 

  27. Zhang, Y. & Tycko, B. Monoallelic expression of the human H19 gene. Nature Genet. 1, 40–44 (1992).

    Article  CAS  PubMed  Google Scholar 

  28. Koufos, A. et al. Familial Wiedemann-Beckwith syndrome and a second Wilms tumor locus both map to 11p15.5. Am. J. hum. Genet. 44, 711–719 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Ping, A.J. et al. Genetic Linkage of Beckwith-Wiedemann syndrome to 11p15. Am. J. hum. Genet. 44, 720–723 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Niikawa, N. et al. The Wiedemann-Beckwith syndrome: pedigree studies on five families with evidence for autosomal dominant inheritance with variable expressivity. Am. J. med. Genet. 24, 41–55 (1986).

    Article  CAS  PubMed  Google Scholar 

  31. Lubinsky, M., Herrmann, J., Kosseff, A.L. & Opitz, J.M. Autosomal dominant sex-dependent transmission of the Wiedemann-Beckwith syndrome. Lancet 1, 983 (1974).

    Google Scholar 

  32. Aleck, K.A. & Hadro, T.A. Dominant inheritance of Wiedemann-Beckwith syndrome: further evidence for transmission of “unstable premutation” through carrier women. Am. J. med. Genet. 33, 155–160 (1989).

    Article  CAS  PubMed  Google Scholar 

  33. Henry, I. et al. Uniparental paternal disomy in a genetic cancer-predisposing syndrome. Nature 351, 665–667 (1991).

    Article  CAS  PubMed  Google Scholar 

  34. Turleau, C. et al. Trisomy 11p15 and Beckwith-Wiedemann syndrome: a report of two cases. Hum. Genet, 67, 219–221 (1984).

    Article  CAS  PubMed  Google Scholar 

  35. Waziri, M., Patil, S.R., Hanson, J.W. & Bartley, J.A. Abnormality of chromosome 11 in patients with features of Beckwith-Wiedemann syndrome. J. Pediatr. 102, 873–876 (1983).

    Article  CAS  PubMed  Google Scholar 

  36. Ferguson-Smith, A.C., Cattanach, B.M., Barton, S.C., Beechey, C.V. & Surani, M.A. Embryological and molecular investigations of parental imprinting on mouse chromosome 7. Nature 351, 667–670 (1991).

    Article  CAS  PubMed  Google Scholar 

  37. Carle, G.F. & Olson, M.V. An electrophoretic karyotype for yeast. Proc. natn. Acad. Sci. U.S.A. 82, 3756–3760 (1985).

    Article  CAS  Google Scholar 

  38. Chu, G., Vollrath, D. & Davis, R.W. Separation of large DNA molecules by contour-clamped homogenous electric fields. Science 234, 1582–1585 (1986).

    Article  CAS  PubMed  Google Scholar 

  39. Church, G.M. & Gilbert, W. Genomic sequencing. Proc. natn. Acad. Sci. U.S.A. 81, 1991–1995 (1984).

    Article  CAS  Google Scholar 

  40. Feinberg, A.P. & Vogelstein, B. A technique for radiolabeling DNA restriction fragments to high specific activity. Anal. Biochem. 137, 266–267 (1984).

    Article  CAS  PubMed  Google Scholar 

  41. Burke, D.T., Carle, G.F. & Olson, M.V. Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science 236, 806–812 (1987).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Molecular Biology, Princeton University, Princeton, New Jersey, 08544, USA

    Sharon Zemel, Marisa S. Bartolomei & Shirley M. Tilghman

Authors
  1. Sharon Zemel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marisa S. Bartolomei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shirley M. Tilghman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zemel, S., Bartolomei, M. & Tilghman, S. Physical linkage of two mammalian imprinted genes, H19 and insulin–like growth factor 2. Nat Genet 2, 61–65 (1992). https://doi.org/10.1038/ng0992-61

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0992-61

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing