生物谷注:小鼠基因组荧光照片。红色是Xist RNA与DNA结合部分,蓝色为小鼠DNA。(图片来源:Nature Publishing Group, Ng, K., et al., Xist and the order of silencing, EMBO reports 8, 34–39.)
雌性哺乳动物携带两个版本的X-染色体,而雄性则携带一个X-染色和一个Y-染色体,为了抵消双剂量同一基因可能产生的毒性,X-染色体上的大多数基因都被沉默。这一X-染色体失活(XCI)过程,长期以来被假设是由RNA基因Xist((X inactivation-specific transcript))的表达、具体来说是由该基因在失活X-染色体上的版本的表达触发的。
在最新一项研究中,美国北卡罗琳娜大学研究人员用小鼠胚胎(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,实际情况更为复杂。事实上,在留下印迹的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。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 460, 647-651 (30 July 2009) | doi:10.1038/nature08161
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
1 Department of Genetics,
2 Carolina Center for Genome Sciences,
3 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7264, USA
4 Correspondence to: Terry Magnuson1,2,3 Correspondence and requests for materials should be addressed to T.M.
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.