Nature：X染色体的RNAi机制

　　

生物通报道，北卡罗来纳大学教堂山分校基因组科学中心，Lineberger癌症综合研究中心，以及遗传学系的科学家在X染色体RNAi机制的最新研究进展，文章Evidence of Xist RNA-independent initiation of mouse imprinted X-chromosome inactivation发表在最近一期的Nature杂志上。

 

通讯作者是北卡罗来大学的Terry Magnuson教授，主要从事表观遗传学、发育与癌症方面的研究。

 

雌性哺乳动物细胞中的性染色体为XX组合，通常为了避免相同基因表达两次带来的毒性作用，有一个X染色体上的同位基因会被沉默掉，这一过程被定义为X染色体失活过程（X-chromosome inactivation，XCI）。

 

XCI是表观遗传学中常见的调节方式。在雌性发育的早期阶段，XCI是一种常见的生物学现象。在真哺乳亚纲动物中，XCI的发生通常伴随着非编码Xist RNA的调节作用，Xist RNA不断的转录出蛋白复合物促进XCI。

 

Terry Magnuson用小鼠胚胎（研究人员用基因工程方法使这些小鼠在其未来失活的X-染色体上含有一个有缺陷的Xist基因）所做的新的研究工作显示，标记的XCI过程中，父系X-染色体的沉默可在没有父系Xist的情况下被启动。如果仍旧没有Xist，X-染色体最终会再活化，说明它的作用也许是使沉默长期保持稳定。

（生物通 小茜）

 

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生物通推荐原文检索：

Evidence of Xist RNA-independent initiation of mouse imprinted X-chromosome inactivation

 

Sundeep Kalantry1,2,3, Sonya Purushothaman1,2,3, Randall Bryant Bowen1,2,3, Joshua Starmer1,2,3 & Terry Magnuson1,2,3

 

Department of Genetics,

Carolina Center for Genome Sciences,

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7264, USA

 

【Abstract】

XX female mammals undergo transcriptional silencing of most genes on one of their two X chromosomes to equalize X-linked gene dosage with XY males in a process referred to as X-chromosome inactivation (XCI). XCI is an example of epigenetic regulation1. Once enacted in individual cells of the early female embryo, XCI is stably transmitted such that most descendant cells maintain silencing of that X chromosome2. In eutherian mammals, XCI is thought to be triggered by the expression of the non-coding Xist RNA from the future inactive X chromosome (Xi)3, 4, 5; Xist RNA in turn is proposed to recruit protein complexes that bring about heterochromatinization of the Xi6, 7. Here we test whether imprinted XCI, which results in preferential inactivation of the paternal X chromosome (Xp), occurs in mouse embryos inheriting an Xp lacking Xist. We find that silencing of Xp-linked genes can initiate in the absence of paternal Xist; Xist is, however, required to stabilize silencing along the Xp. Xp-linked gene silencing associated with mouse imprinted XCI, therefore, can initiate in the embryo independently of Xist RNA.