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.

  • Research Highlight
  • Published:

Epigenetics

Imprinting links embryogenesis and tumour formation

Nature Reviews Genetics volume 7, pages 904–905 (2006)Cite this article

Although the misregulation of imprinted loci leads to developmental abnormalities in humans, biological functions are known for only a handful of imprinted genes. Motivated by this gap in our knowledge, Varrault et al. studied a maternally imprinted gene, Zac1 , which encodes a zinc-finger transcription factor that induces apoptosis and cell-cycle arrest. Knocking out Zac1 resulted in fetal growth restriction in pups of Zac1−/− and Zac1+/− mice that received their knockout allele from the father (in the mother, Zac1 is inactive anyway). Interestingly, this phenotype is counterintuitive from the point of view of the function of Zac1 as a tumour suppressor gene (its loss should facilitate growth), although it is consistent with a paternally expressed imprinted gene (such genes are thought to promote fetal growth).

But Zac1 knockouts also had ossification defects and other morphological abnormalities, and many pups died postnatally as a result of lung abnormalities. To understand the underlying mechanisms, the authors performed a meta-analysis of 116 mouse microarray data sets to look for genes that are co-regulated with Zac1, assuming that genes that cluster together might share biological function. The set of genes that were most closely linked to Zac1 was enriched in imprinted genes, including H19 , insulin-like growth factor 2 ( Igf2 ), insulin-like growth factor 2 receptor ( Igf2r ) and others. The phenotypes of mutants in many of these genes, including Zac1, indicate that these genes form an imprinted gene network (IGN) that controls embryonic growth and differentiation.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

References

ORIGINAL RESEARCH PAPER

  1. Varrault, A. et al. Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth. Dev. Cell 11, 711–722 (2006)

    Article  CAS  Google Scholar 

FURTHER READING

  1. Reik, W. & Lewis, A. Co-evolution of X-chromosome inactivation and imprinting in mammals. Nature Rev. Genet. 6, 403–410 (2005)

    Article  CAS  Google Scholar 

  2. Barabasi, A.-L. & Oltvai, Z. N. Network biology: understanding the cell's functional organization. Nature Rev. Genet. 5, 101–113 (2004)

    Article  CAS  Google Scholar 

Download references

Authors
  1. Magdalena Skipper
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Skipper, M. Imprinting links embryogenesis and tumour formation. Nat Rev Genet 7, 904–905 (2006). https://doi.org/10.1038/nrg2021

Download citation

  • Issue date:

  • DOI: https://doi.org/10.1038/nrg2021

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