PGC7/Stella protects against DNA demethylation in early embryogenesis

Toshinobu Nakamura, Yoshikazu Arai, Hiroki Umehara, Masaaki Masuhara, Tohru Kimura, Hisaaki Taniguchi, Toshihiro Sekimoto, Masahito Ikawa, Yoshihiro Yoneda, Masaru Okabe, Satoshi Tanaka, Kunio Shiota, Toru Nakano

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DNA methylation is an important means of epigenetic gene regulation 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 fertilization, 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.

元の言語English
ページ(範囲)64-71
ページ数8
ジャーナルNature Cell Biology
9
発行部数1
DOI
出版物ステータスPublished - 2007 1
外部発表Yes

ASJC Scopus subject areas

  • Cell Biology

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    Nakamura, T., Arai, Y., Umehara, H., Masuhara, M., Kimura, T., Taniguchi, H., Sekimoto, T., Ikawa, M., Yoneda, Y., Okabe, M., Tanaka, S., Shiota, K., & Nakano, T. (2007). PGC7/Stella protects against DNA demethylation in early embryogenesis. Nature Cell Biology, 9(1), 64-71. https://doi.org/10.1038/ncb1519