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タイトル: Synergy of Eed and Tsix in the repression of Xist gene and X-chromosome inactivation
著者: Shibata, Shinwa
Yokota, Takashi link image link image
Wutz, Anton
柴田, 進和
横田, 崇
発行日: 2008年 7月 9日
出版社(者): Nature Publishing Group
雑誌名: EMBO Journal
ISSN: 0261-4189
巻: 27
号: 13
開始ページ: 1816
終了ページ: 1826
キーワード: Antisense
DNA methylation
Eed
Histone modification
Xist
抄録: X-chromosome inactivation (XCI) depends on the noncoding Xist gene. Xist transcription is negatively regulated by its antisense partner Tsix, whose disruption results in nonrandom XCI in females. However, males can maintain Xist in a repressed state without Tsix, indicating participation of additional factor(s) in the protection of the single male X from inactivation. Here, we provide evidence that the histone methyltransferase Eed is also involved in the process. Male embryonic stem cells with Eed-null and Tsix mutations (X ΔY Eed-/-) showed Xist hyperactivation upon differentiation, whereas cells with either mutation alone did not. Impaired X-linked gene expression was observed in the XΔY Eed-/- ES cells at the onset of differentiation. The Xist promoter in the XΔY Eed-/- cells showed elevated histone H3-dimethyl lysine 4 modifications and lowered CpG methylation, which are characteristics of open chromatin. Hence, we identified Eed as an additional major player in the regulation of Xist expression. The synergy of Polycomb group proteins and antisense Tsix transcription in Xist gene regulation explains why males can repress Xist without Tsix. © 2008 European Molecular Biology Organization | All Rights Reserved.
DOI: 10.1038/emboj.2008.110
URI: http://hdl.handle.net/2297/11564
資料種別: Journal Article
版表示: author
出現コレクション:1. 査読済論文(医学・保健)

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