生物谷注:小鼠基因組熒光照片,。紅色是Xist RNA與DNA結(jié)合部分,,藍色為小鼠DNA,。(圖片來源:Nature Publishing Group, Ng, K., et al., Xist and the order of silencing, EMBO reports 8, 34–39.)
雌性哺乳動物攜帶兩個版本的X-染色體,,而雄性則攜帶一個X-染色和一個Y-染色體,,為了抵消雙劑量同一基因可能產(chǎn)生的毒性,,X-染色體上的大多數(shù)基因都被沉默。這一X-染色體失活(XCI)過程,,長期以來被假設是由RNA基因Xist((X inactivation-specific transcript))的表達,、具體來說是由該基因在失活X-染色體上的版本的表達觸發(fā)的。
在最新一項研究中,,美國北卡羅琳娜大學研究人員用小鼠胚胎(研究人員用基因工程方法使這些小鼠在其未來失活的X-染色體上含有一個有缺陷的Xist基因)所做的新的研究工作顯示,,實際情況更為復雜。事實上,,在留下印跡的XCI過程中,,父系X-染色體的沉默可在沒有父系Xist的情況下被啟動。如果仍舊沒有Xist,,X-染色體最終會再活化,,說明它的作用也許是使沉默長期保持穩(wěn)定。(生物谷Bioon.com)
生物谷推薦原始出處:
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.