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.

  • Letter
  • Published:

An imprinting element from the mouse H19 locus functions as a silencer in Drosophila

Nature Genetics volume 16, pages 171–173 (1997)Cite this article

Abstract

Genomic imprinting as originally described in Sciara1 is displayed by many organisms. In mammals, X-inactivation and the parent-of-origin-specific silencing of imprinted genes are examples of this phenomenon2,3. A heritable chromatin structural modification may be the critical mechanism in such instances of chromosome condensation and preferential gene inactivation. H19 is an imprinted gene4 in which the repressed paternal allele is hypermethylated and the compacted chromatin is relatively resistant to digestion by nucleases5–7. In order to uncover underlying conserved epigenetic mechanisms we have introduced a mouse H19 transgene into Drosophila. We show here that a 1.2-kb H19 upstream sequence functions in cis as a parent-of-origin independent silencing element in Drosophila. Strikingly, this cis-acting element is located within an upstream region that is necessary for H19 imprinting in mice8. These results suggest involvement of an evolutionary conserved mechanism in both gene silencing in Drosophila and imprinting in mice.

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. Crouse, H.V. The controlling element in sex chromosome behaviour in Sciara. Genetics 45, 1429–1443 (1960).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Efstratiadis, A. Parental imprinting of autosomal mammalian genes. Curr. Opin. Genet. Dev. 4, 265–280 (1994).

    Article  CAS  PubMed  Google Scholar 

  3. John, R.M. & Surani, M.A. Imprinted genes and regulation of gene expression by epigenetic inheritance. Curr. Opin. Cell Biol. 8, 348–353 (1996).

    Article  CAS  PubMed  Google Scholar 

  4. 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 

  5. Bartolomei, M.S., Webber, A.L., Brunkow, M.E. & Tilghman, S.M. Epigenetic mechanisms underlying the imprinting of the mouse H19 gene. Genes Dev. 7, 1663–1673 (1993).

    Article  CAS  PubMed  Google Scholar 

  6. Ferguson-Smith, A.C., Sasaki, H., Cattanach, B.M. & Surani, M.A. Parental-origin-specific epigenetic modification of the mouse H19 gene. Nature 362, 751–755 (1993).

    Article  CAS  PubMed  Google Scholar 

  7. Li, E., Beard, C. & Jaenisch, R. Role for DNA methylation in genomic imprinting. Nature 366, 362–365 (1993).

    Article  CAS  PubMed  Google Scholar 

  8. Elson, D.A. & Bartolomei, M.S. A 5′ differentially methylated sequence and the 3′ flanking region are necessary for HI9 transgene imprinting. Mol. Cell. Biol. 17, 309–317 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Leighton, P.A., Ingram, R.S., Eggenschwiler, J., Efstratiadis, A. & Tilghman, S.M. Disruption of imprinting caused by deletion of the H19 gene region in mice. Nature 375, 34–39 (1995).

    Article  CAS  PubMed  Google Scholar 

  10. Urieli-Shoval, S., Gruenbaum, Y., Sedat, J. & Razin, A. The absence of detectable methylated bases in Drosophila melanogaster DNA. FEBS Lett. 146, 148–152 (1982).

    Article  CAS  PubMed  Google Scholar 

  11. Patel, C.V. & Gopinathan, K.P. Determination of trace amounts of 5-methylcytosine in DNA by reverse-phase high-performance liquid chromatography. Anal. Biochem. 164, 164–169 (1987).

    Article  CAS  PubMed  Google Scholar 

  12. Yoo-Warren, H., Pachnis, V., Ingram, R.S. & Tilghman, S.M. Two regulatory domains flank the mouse tf H19 gene. Mol. Cell. Biol. 8, 4707–4715 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Robertson, H.M. et al. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics 118, 461–470 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Daniels, S.B., McCarron, M., Love, C. & Chovnick, A. Dysgenesis-induced instability of rosy locus transformation in Drosophila melanogaster. analysis of excision events and the selective recovery of control element deletions. Genetics 109, 95–117 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Tremblay, K.D., Saam, J.R., Ingram, R.S., Tilghman, S.M. & Bartolomei, M.S. A paternal-specific methylation imprint marks the alleles of the mouse H19 gene. Nature Genet. 9, 407–413 (1995).

    Article  CAS  PubMed  Google Scholar 

  16. Zink, D. & Paro, R. Drosophila Polycomb-group regulated chromatin inhibits the accessibility of a trans-activator to its target DNA. EMBO J. 14, 5660–5671 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pirrotta, V. in Vectors: A survey of molecular cloning vectors and their uses (eds Rodriguez, R.L. & Denhardt, D.T.) 437–456 (Butterworths, Boston, 1988).

    Book  Google Scholar 

  18. Messmer, S., Franke, A. & Paro, R. Analysis of the functional role of the Polycomb chromo domain in Drosophila. Genes Dev. 6, 1241–1254 (1992).

    Article  CAS  PubMed  Google Scholar 

  19. Spradling, A.L. & Rubin, G.M. Transformation of cloned P elements into Drosophila germ line chromosomes. Science 218, 341–347 (1982).

    Article  CAS  PubMed  Google Scholar 

  20. Sambrook, J., Fritsch, E.F. & Maniatis, T. Molecular cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1989).

    Google Scholar 

  21. Reuter, G. & Wolff, I. Isolation of dominant suppressor mutations for position-effect variegation in Drosophila melanogaster. Mol. Gen. Genet. 182, 516–519 (1981).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Renato Paro: ZMBH, University Heidelberg, Postfach 106249, 69052, Heidelberg, Germany

Authors and Affiliations

  1. ZMBH, University of Heidelberg, Im Neuenheimer Feld 282, 69120, Heidelberg, Germany

    Frank Lyko & Renato Paro

  2. Wellcome/CRC Institute of Cancer and Developmental Biology, Tennis Court Road, Cambridge, CB21QR

    James D. Brenton & M. Azim Surani

  3. Physiological Laboratory, University of Cambridge, CB23EG, U.K.

    James D. Brenton & M. Azim Surani

Authors
  1. Frank Lyko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James D. Brenton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Azim Surani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Renato Paro
    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

Lyko, F., Brenton, J., Surani, M. et al. An imprinting element from the mouse H19 locus functions as a silencer in Drosophila. Nat Genet 16, 171–173 (1997). https://doi.org/10.1038/ng0697-171

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0697-171

This article is cited by

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