Meiotic sex chromosome inactivation in male mice with targeted disruptions of Xist

Meiotic sex chromosome inactivation in male mice with targeted disruptions of Xist
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DOI:
10.1242/jcs.00111
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发表时间:
2002-11
影响因子:
4
通讯作者:
James M. A. Turner;S. Mahadevaiah;D. Elliott;H. Garchon;J. Pehrson;R. Jaenisch;P. Burgoyne
James M. A. Turner;S. Mahadevaiah;D. Elliott;H. Garchon;J. Pehrson;R. Jaenisch;P. Burgoyne
中科院分区:
生物学2区
文献类型:
--
作者:
James M. A. Turner;S. Mahadevaiah;D. Elliott;H. Garchon;J. Pehrson;R. Jaenisch;P. Burgoyne

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X染色体失活在胎盘哺乳动物的生命周期中发生两次。在正常女性中,每个细胞中的一条 X 染色体在胚胎发生早期失活,而在男性中,X 染色体与生精细胞中的 Y 染色体一起在早期减数分裂前期之前或期间失活。雌性体细胞中一条 X 染色体的失活有助于平衡雄性和雌性之间的 X 连锁基因剂量,但雄性减数分裂性染色体失活 (MSCI) 的作用尚不清楚。体细胞和雄性减数分裂细胞的失活X染色体具有相似的特性,例如组蛋白macroH2A1.2的晚期复制和富集,表明失活的共同机制。这种可能性得到了以下事实的支持:介导体细胞 X 失活的 Xist RNA 在雄性小鼠和人类的睾丸中表达。在本研究中,我们发现 Xist RNA 和 Tsix RNA(一种控制体细胞 Xist 功能的反义 RNA)在睾丸中以生殖细胞依赖性方式表达。然而,我们发现,在具有阻止体细胞 X 失活的 Xist 靶向突变的小鼠中,MSCI 和性体形成没有改变,这表明体细胞 X 失活和 MSCI 通过根本不同的机制发生。
X chromosome inactivation occurs twice during the life cycle of placental mammals. In normal females, one X chromosome in each cell is inactivated early in embryogenesis, while in the male, the X chromosome is inactivated together with the Y chromosome in spermatogenic cells shortly before or during early meiotic prophase. Inactivation of one X chromosome in somatic cells of females serves to equalise X-linked gene dosage between males and females, but the role of male meiotic sex chromosome inactivation (MSCI) is unknown. The inactive X-chromosome of somatic cells and male meiotic cells share similar properties such as late replication and enrichment for histone macroH2A1.2, suggesting a common mechanism of inactivation. This possibility is supported by the fact that Xist RNA that mediates somatic X-inactivation is expressed in the testis of male mice and humans. In the present study we show that both Xist RNA and Tsix RNA, an antisense RNA that controls Xist function in the soma, are expressed in the testis in a germ-cell-dependent manner. However, our finding that MSCI and sex-body formation are unaltered in mice with targeted mutations of Xist that prevent somatic X inactivation suggests that somatic X-inactivation and MSCI occur by fundamentally different mechanisms.