PGC7/Stella protects against DNA demethylation in early embryogenesis (original) (raw)

Nature Cell Biology volume 9, pages 64–71 (2007)Cite this article

Abstract

DNA methylation is an important means of epigenetic gene regulation1,2 and must be carefully controlled as a prerequisite for normal early embryogenesis. Although global demethylation occurs soon after fertilization, it is not evenly distributed throughout the genome. Genomic imprinting and epigenetic asymmetry between parental genomes, that is, delayed demethylation of the maternal genome after fertilization3,4,5,6, are clear examples of the functional importance of DNA methylation. Here, we show that PGC7/Stella, a maternal factor essential for early development, protects the DNA methylation state of several imprinted loci and epigenetic asymmetry. After determining that PGC7/Stella binds to Ran binding protein 5 (RanBP5; a nuclear transport shuttle protein), mutant versions of the two proteins were used to examine exactly when and where PGC7/Stella functions within the cell. It is likely that PGC7/Stella protects the maternal genome from demethylation only after localizing to the nucleus, where it maintains the methylation of several imprinted genes. These results demonstrate that PGC7/Stella is indispensable for the maintenance of methylation involved in epigenetic reprogramming after fertilization.

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Acknowledgements

We thank M. Sato for an initial contribution to this study, and. H. Niwa, K. Nakayama and T. A. Van Dyke for providing plasmids. We also thank Y. Fujita, M. Ikeuchi and N. Asada for assistance, and A. Mizokami for secretarial assistance. This work was supported in part by grants from the Ministry of Education, Science, Sports, Culture, and Technology; the Support Program for Technology Development on the Basis of Academic Findings (NEDO); the Uehara Memorial Foundation; the Osaka Cancer Foundation; and the 21st Century COE “CICET”.

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Authors and Affiliations

  1. Department of Pathology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan
    Toshinobu Nakamura, Hiroki Umehara, Tohru Kimura & Toru Nakano
  2. Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo, 113-8657, Japan
    Yoshikazu Arai, Satoshi Tanaka & Kunio Shiota
  3. Department of Oral Anatomy, Meikai University School of Dentistry, Saitama, 350-0283, Japan
    Masaaki Masuhara
  4. Institute for Enzyme Research, The University of Tokushima, Tokushima, 770-8503, Japan
    Hisaaki Taniguchi
  5. Department of Cell Biology and Neuroscience, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan
    Toshihiro Sekimoto
  6. Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan
    Masahito Ikawa & Masaru Okabe
  7. Department of Frontier Biosciences, Graduate School of Frontier Bioscience,
    Yoshihiro Yoneda
  8. Osaka University, Osaka, 565-0871, Japan
    Yoshihiro Yoneda
  9. Genome Information Research Center, Osaka University, Osaka, 565-0871, Japan
    Masaru Okabe

Authors

  1. Toshinobu Nakamura
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  2. Yoshikazu Arai
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  3. Hiroki Umehara
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  4. Masaaki Masuhara
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  5. Tohru Kimura
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  6. Hisaaki Taniguchi
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  7. Toshihiro Sekimoto
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  8. Masahito Ikawa
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  9. Yoshihiro Yoneda
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  10. Masaru Okabe
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  11. Satoshi Tanaka
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  12. Kunio Shiota
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  13. Toru Nakano
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Correspondence toToru Nakano.

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Nakamura, T., Arai, Y., Umehara, H. et al. PGC7/Stella protects against DNA demethylation in early embryogenesis.Nat Cell Biol 9, 64–71 (2007). https://doi.org/10.1038/ncb1519

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