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.

Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality

Nature Genetics volume 38, pages 101–106 (2006)Cite this article

Abstract

By comparing mammalian genomes, we and others have identified actively transcribed Ty3/gypsy retrotransposon-derived genes with highly conserved DNA sequences and insertion sites1,2,3,4,5,6. To elucidate the functions of evolutionarily conserved retrotransposon-derived genes in mammalian development, we produced mice that lack one of these genes, Peg10 (paternally expressed 10)1,2,3,7, which is a paternally expressed imprinted gene on mouse proximal chromosome 6. The Peg10 knockout mice showed early embryonic lethality owing to defects in the placenta. This indicates that Peg10 is critical for mouse parthenogenetic development and provides the first direct evidence of an essential role of an evolutionarily conserved retrotransposon-derived gene in mammalian development.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

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

Figure 1: Targeted disruption of the Peg10 locus.
Figure 2: Peg10 knockout embryos show severe growth retardation and placental defects.
Figure 3: Rescue of Peg10 Pat-KO embryos by tetraploid wild-type extraembryonic tissues.
Figure 4: Partial pedigrees of Peg10 knockout mice and their normal imprinting status.
Figure 5: Relative expression levels of Peg10, Sgce and Ppp1r9a at different stages, as determined by quantitative RT-PCR.

References

  1. Ono, R. et al. A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21. Genomics 73, 232–237 (2001).

    Article  CAS  PubMed  Google Scholar 

  2. Volff, J., Korting, C. & Schartl, M. Ty3/Gypsy retrotransposon fossils in mammalian genomes: did they evolve into new cellular functions? Mol. Biol. Evol. 18, 266–270 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Butler, M., Goodwin, T., Simpson, M., Singh, M. & Poulter, R. Vertebrate LTR retrotransposons of the Tf1/sushi group. J. Mol. Evol. 52, 260–274 (2001).

    Article  CAS  PubMed  Google Scholar 

  4. Charlier, C. et al. Human-ovine comparative sequencing of a 250-kb imprinted domain encompassing the callipyge (clpg) locus and identification of six imprinted transcripts: DLK1, DAT, GTL2, PEG11, antiPEG11, and MEG8. Genome Res. 11, 850–862 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lynch, C. & Tristem, M. A co-opted gypsy-type LTR-retrotransposon is conserved in the genomes of humans, sheep, mice, and rats. Curr. Biol. 13, 1518–1523 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Seitz, H. et al. Imprinted microRNA genes transcribed antisense to a reciprocally imprinted retrotransposon-like gene. Nat. Genet. 34, 261–262 (2003).

    Article  CAS  PubMed  Google Scholar 

  7. Shigemoto, K. et al. Identification and characterisation of a developmentally regulated mammalian gene that utilises -1 programmed ribosomal frameshifting. Nucleic Acids Res. 29, 4079–4088 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ono, R. et al. Identification of a large novel imprinted gene cluster on mouse proximal chromosome 6. Genome Res. 13, 1696–1705 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Poulter, R. & Butler, M. A retrotransposon family from the pufferfish (fugu) Fugu rubripes. Gene 215, 241–249 (1998).

    Article  CAS  PubMed  Google Scholar 

  10. Beechey, C., Cattanach, B.M., Blake, A. & Peters, J. Mouse Imprinting Data and References, http://www.mgu.har.mrc.ac.uk/research/imprinting (2003).

  11. Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W. & Roder, J.C. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc. Natl. Acad. Sci. USA 90, 8424–8428 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Guillemot, F. et al. Genomic imprinting of Mash2, a mouse gene required for trophoblast development. Nat. Genet. 9, 235–242 (1995).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. McGrath, J. & Solter, D. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37, 179–183 (1984).

    Article  CAS  PubMed  Google Scholar 

  15. Sturm, K.S., Flannery, M.L. & Pedersen, R.A. Abnormal development of embryonic and extraembryonic cell lineages in parthenogenetic mouse embryos. Dev. Dyn. 201, 11–28 (1994).

    Article  CAS  PubMed  Google Scholar 

  16. Moore, T. & Haig, D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet. 7, 45–49 (1991).

    Article  CAS  PubMed  Google Scholar 

  17. Constancia, M. et al. Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature 417, 945–948 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Agrawal, A., Eastman, Q.M. & Schatz, D.G. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 394, 744–751 (1998).

    Article  CAS  PubMed  Google Scholar 

  19. Nakamura, T.M. & Cech, T.R. Reversing time: origin of telomerase. Cell 92, 587–590 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. Smit, A.F. Interspersed repeats and other mementos of transposable elements in mammalian genomes. Curr. Opin. Genet. Dev. 9, 657–663 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. Toh, H., Ono, M. & Miyata, T. Retroviral gag and DNA endonuclease coding sequences in IgE-binding factor gene. Nature 318, 388–389 (1985).

    Article  CAS  PubMed  Google Scholar 

  22. Mi, S. et al. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403, 785–789 (2000).

    Article  CAS  PubMed  Google Scholar 

  23. Dupressoir, A. et al. Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae. Proc. Natl. Acad. Sci. USA 102, 725–730 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tsou, A.P. et al. Overexpression of a novel imprinted gene, PEG10, in human hepatocellular carcinoma and in regenerating mouse livers. J. Biomed. Sci. 10, 625–635 (2003).

    CAS  PubMed  Google Scholar 

  25. Okabe, H. et al. Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1. Cancer Res. 63, 3043–3048 (2003).

    CAS  PubMed  Google Scholar 

  26. Lux, A. et al. Human retroviral gag- and gag-pol-like proteins interact with the TGF-β receptor ALK1. J. Biol. Chem. 280, 8482–8493 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Hedges, S.B. The origin and evolution of model organisms. Nat. Rev. Genet. 3, 838–849 (2002).

    Article  CAS  PubMed  Google Scholar 

  28. Nagasaki, K. et al. Identification of a novel gene, LDOC1, down-regulated in cancer cell lines. Cancer Lett. 140, 227–234 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Brandt, J. et al. Transposable elements as a source of genetic innovation: expression and evolution of a family of retrotransposon-derived neogenes in mammals. Gene 345, 101–111 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Horike, S., Cai, S., Miyano, M., Cheng, J.F. & Kohwi-Shigematsu, T. Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nat. Genet. 37, 31–40 (2005).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank M.A. Surani and S. Barton for helpful suggestions on this manuscript. We also thank S. Aizawa for providing the DT-A vector, J. Miyazaki for the Cre-recombinase expression vector, E. Robertson for the CCE ES cells, H. Sasaki for the Gallus gallus genome, Y. Nakahara and M. Takabe of the Mitsubishi Kagaku Institute of Life Sciences for animal breeding, and S. Ichinose and T. Tajima of Tokyo Medical and Dental University and N. Kawabe and H. Hasegawa of Tokai University for assistance with the in situ hybridization experiments. This work was supported by grants from Research Fellowships of the Japan Society for the Promotion of Science for young Scientists (JSPS) to R.O.; the Asahi Glass Foundation to T.K.-I.; and CREST (the research program of the Japan Science and Technology Agency (JST)), the Uehara Memorial Science Foundation, the Ministry of Health, Labour and Welfare for Child Health and Development (14-C) and the Ministry of Education, Culture, Sports, Science and Technology of Japan to F.I.

Author information

Author notes

  1. Minesuke Yokoyama

    Present address: Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Niigata, 951-8585, Japan

Authors and Affiliations

  1. Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan

    Ryuichi Ono, Mie Naruse, Noriko Wakisaka-Saito, Takashi Kohda & Fumitoshi Ishino

  2. CREST, Japan Science and Technology Agency (JST), 4-1-8 Hon-machi, Kawaguchi, 332-0011, Saitama, Japan

    Ryuichi Ono, Kimiko Inoue, Noriko Wakisaka-Saito, Takashi Kohda, Atsuo Ogura, Minesuke Yokoyama, Tomoko Kaneko-Ishino & Fumitoshi Ishino

  3. Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo, 194-8511, Japan

    Kenji Nakamura, Toshiaki Hino, Rika Suzuki-Migishima & Minesuke Yokoyama

  4. BioResource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan

    Kimiko Inoue, Narumi Ogonuki, Hiromi Miki & Atsuo Ogura

  5. Facility for Recombinant Mice, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan

    Takako Usami

  6. Division for Gene Research, Center for Biological Resources and Informatics, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan

    Noriko Wakisaka-Saito

  7. School of Health Sciences, Tokai University, Bohseidai, Isehara, Kanagawa, 259-1193, Japan

    Noriko Wakisaka-Saito & Tomoko Kaneko-Ishino

Authors
  1. Ryuichi Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenji Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kimiko Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mie Naruse
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takako Usami
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Noriko Wakisaka-Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toshiaki Hino
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rika Suzuki-Migishima
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Narumi Ogonuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hiromi Miki
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Takashi Kohda
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Atsuo Ogura
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Minesuke Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Tomoko Kaneko-Ishino
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Fumitoshi Ishino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Tomoko Kaneko-Ishino or Fumitoshi Ishino.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Placental morphology is normal until 8.5 d.p.c. (PDF 2856 kb)

Supplementary Fig. 2

Fetal-to-placental weight ratios. (PDF 90 kb)

Supplementary Fig. 3

Production of Peg10 loxP KO mice, partial pedigrees of the Peg10 loxP KO mice and the relative expression levels of Peg10 Pat-loxP-KO embryos. (PDF 604 kb)

Supplementary Fig. 4

Peg10 loxP KO embryos show severe growth retardation and placental defects. (PDF 2205 kb)

Supplementary Fig. 5

Rescue of Peg10 Pat-KO embryos by tetraploid wild-type extraembryonic tissues. (PDF 1261 kb)

Supplementary Fig. 6

Expression profile of Ascl2 in Peg10 Pat-KO placentas. (PDF 135 kb)

Supplementary Fig. 7

Comparative genomic analysis of Sgce and Ppp1r9a. (PDF 180 kb)

Supplementary Table 1

Lethality of Peg10 lox-P KO (Pat-lox-P KO) fetuses (PDF 69 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ono, R., Nakamura, K., Inoue, K. et al. Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality. Nat Genet 38, 101–106 (2006). https://doi.org/10.1038/ng1699

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1699

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