Role of smcHD1 in establishment of epigenetic states required for the maintenance of the x-inactivated state in mice

Yuki Sakakibara, Koji Nagao, Marnie Blewitt, Hiroyuki Sasaki, Chikashi Obuse, Takashi Sado

研究成果: Contribution to journalArticle査読

8 被引用数 (Scopus)

抄録

X inactivation in mammals is regulated by epigenetic modifications. Functional deficiency of SmcHD1 has been shown to cause de-repression of X-inactivated genes in post-implantation female mouse embryos, suggesting a role of SmcHD1 in the maintenance of X inactivation. Here, we show that de-repression of X-inactivated genes accompanied a local reduction in the enrichment of H3K27me3 in mouse embryonic fibroblasts deficient for SmcHD1. Furthermore, many of these genes overlapped with those having a significantly lower enrichment of H3K27me3 at the blastocyst stage in wild type. Intriguingly, however, depletion of SmcHD1 did not compromise the X-inactivated state in immortalized female mouse embryonic fibroblasts, in which X inactivation had been established and maintained. Taking all these findings together, we suggest that SmcHD1 facilitates the incorporation of H3K27me3 and perhaps other epigenetic modifications at gene loci that are silenced even with the lower enrichment of H3K27me3 at the early stage of X inactivation. The epigenetic state at these loci would, however, remain as it is at the blastocyst stage in the absence of SmcHD1 after implantation, which would eventually compromise the maintenance of the X-inactivated state at later stages.

本文言語英語
論文番号dev166462
ジャーナルDevelopment (Cambridge)
145
18
DOI
出版ステータス出版済み - 9 2018

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 発生生物学

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