Development Genes and Evolution

, Volume 207, Issue 8, pp 551–561

Epigenotype switching of imprintable loci in embryonic germ cells

  • T. Tada
  • M. Tada
  • Kathy Hilton
  • Sheila C. Barton
  • Takashi Sado
  • Nobuo Takagi
  • M. A. Surani
ORIGINAL ARTICLE

DOI: 10.1007/s004270050146

Cite this article as:
Tada, T., Tada, M., Hilton, K. et al. Dev Gene Evol (1998) 207: 551. doi:10.1007/s004270050146

Abstract

 Expression of imprinted genes is dependent on their parental origin. This is reflected in the heritable differential methylation of parental alleles. The gametic imprints are however reversible as they do not endure for more than one generation. To investigate if the epigenetic changes in male and female germ line are similar or not, we derived embryonic germ (EG) cells from primordial germ cells (PGCs) of day 11.5 and 12.5 male and female embryos. The results demonstrate that they have an equivalent epigenotype. First, chimeras made with EG cells derived from both male and female embryos showed comparable fetal overgrowth and skeletal abnormalities, which are similar to but less severe than those induced by androgenetic embryonic stem (ES) cells. Thus, EG cells derived from female embryos resemble androgenetic ES cells more than parthenogenetic cells. Furthermore, the methylation status of both alleles of a number of loci in EG cells was similar to that of the paternal allele in normal somatic cells. Hence, both alleles of Igf2r region 2, Peg1/Mest, Peg3, Nnat were consistently unmethylated in EG cells as well as in the primary embryonic fibroblasts (PEFs) rescued from chimeras. More strikingly, both alleles of p57kip2 that were also unmethylated in EG cells, underwent de novo methylation in PEFs to resemble a paternal allele in somatic cells. The exceptions were the H19 and Igf2 genes that retained the methylation pattern in PEFs as seen in normal somatic tissues. These studies suggest that the initial epigenetic changes in germ cells of male and female embryos are similar.

Key words Germ cell Imprinted genes DNA methylation Chimera Mouse 

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • T. Tada
    • 1
  • M. Tada
    • 1
  • Kathy Hilton
    • 1
  • Sheila C. Barton
    • 1
  • Takashi Sado
    • 2
  • Nobuo Takagi
    • 2
  • M. A. Surani
    • 1
  1. 1.Wellcome/CRC Institute of Cancer and Developmental Biology and Physiological Laboratory, University of Cambridge, Cambridge CB2 1QR, UKGB
  2. 2.Research Center for Molecular Genetics and Division of Biological Sciences, Graduate School of Environmental Earth Science, Hokkaido University, JapanJP