Research Abstract


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

2014年11月14日 Nature Communications 5 : 5464 doi: 10.1038/ncomms6464


福田 篤1, 冨川 順子2, 三浦 巧1, 秦 健一郎2, 中林 一彦2, ケビン イーガン3, 阿久津 英憲1 & 梅澤 明弘1

  1. 国立成育医療研究センター 再生医療センター 生殖・細胞医療研究部
  2. 国立成育医療研究センター周産期病態研究部
  3. ハーバード大学幹細胞研究所(アメリカ)
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.