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The role of maternal-specific H3K9me3 modification in establishing imprinted X-chromosome inactivation and embryogenesis in mice

Author

Listed:
  • Atsushi Fukuda

    (National Research Institute for Child Health and Development)

  • Junko Tomikawa

    (National Research Institute for Child Health and Development)

  • Takumi Miura

    (National Research Institute for Child Health and Development)

  • Kenichiro Hata

    (National Research Institute for Child Health and Development)

  • Kazuhiko Nakabayashi

    (National Research Institute for Child Health and Development)

  • Kevin Eggan

    (The Howard Hughes Medical Institute, Harvard University)

  • Hidenori Akutsu

    (National Research Institute for Child Health and Development)

  • Akihiro Umezawa

    (National Research Institute for Child Health and Development)

Abstract

Maintaining a single active X-chromosome by repressing Xist is crucial for embryonic development in mice. Although the Xist activator RNF12/RLIM is present as a maternal factor, maternal Xist (Xm-Xist) is repressed during preimplantation phases to establish imprinted X-chromosome inactivation (XCI). Here we show, using a highly reproducible chromatin immunoprecipitation method that facilitates chromatin analysis of preimplantation embryos, that H3K9me3 is enriched at the Xist promoter region, preventing Xm-Xist activation by RNF12. The high levels of H3K9me3 at the Xist promoter region are lost in embryonic stem (ES) cells, and ES-cloned embryos show RNF12-dependent Xist expression. Moreover, lack of Xm-XCI in the trophectoderm, rather than loss of paternally expressed imprinted genes, is the primary cause of embryonic lethality in 70–80% of parthenogenotes immediately after implantation. This study reveals that H3K9me3 is involved in the imprinting that silences Xm-Xist. Our findings highlight the role of maternal-specific H3K9me3 modification in embryo development.

Suggested Citation

  • Atsushi Fukuda & Junko Tomikawa & Takumi Miura & Kenichiro Hata & Kazuhiko Nakabayashi & Kevin Eggan & Hidenori Akutsu & Akihiro Umezawa, 2014. "The role of maternal-specific H3K9me3 modification in establishing imprinted X-chromosome inactivation and embryogenesis in mice," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6464
    DOI: 10.1038/ncomms6464
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