Incomplete X-inactivation initiated by a hypomorphic Xist allele in the mouse

Yuko Hoki, Rieko Ikeda, Nathan Mise, Yuka Sakata, Tatsuya Ohhata, Hiroyuki Sasaki, Kuniya Abe, Takashi Sado

    研究成果: Contribution to journalArticle査読

    16 被引用数 (Scopus)

    抄録

    X chromosome inactivation (X-inactivation) in female mammals is triggered by differential upregulation of the Xist gene on one of the two X chromosomes and subsequent coating of the X in cis with its non-coding transcripts. Although targeted mutation has clearly shown that Xist is essential for X-inactivation in cis, the molecular mechanism by which Xist RNA induces chromosome silencing is largely unknown. Here, we demonstrate that an Xist mutant generated previously in mouse by gene targeting, XistIVS, is unique in that it partially retains the capacity to silence the X chromosome. Although XistIVS is differentially upregulated and its mutated transcript coats the X chromosome in cis in embryonic and extra-embryonic tissues, X-inactivation thus initiated does not seem to be fully established. The state of such incomplete inactivation is probably unstable and the mutated X is apparently reactivated in a subset of extra-embryonic tissues and, perhaps, early epiblastic cells. XistIVS, which can be referred to as a partial loss-of-function mutation, would provide an opportunity to dissect the molecular mechanism of Xist RNA-mediated chromosome silencing.

    本文言語英語
    ページ(範囲)2649-2659
    ページ数11
    ジャーナルDevelopment
    138
    13
    DOI
    出版ステータス出版済み - 7 1 2011

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Developmental Biology

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