Zhang Li-Feng, Huynh Khanh D, Lee Jeannie T
Howard Hughes Medical Institute, Boston, MA 02114 USA.
Cell. 2007 May 18;129(4):693-706. doi: 10.1016/j.cell.2007.03.036.
In mammalian females, two X chromosomes are epigenetically distinguished as active and inactive chromosomes to balance X-linked gene dosages between males and females. How the Xs are maintained differently in the same nucleus remains unknown. Here, we demonstrate that the inactive X (Xi) is targeted to a distinct nuclear compartment following pairing with its homologous partner. During mid-to-late S phase, 80%-90% of Xi contact the nucleolus and reside within a Snf2h-enriched ring. Autosomes carrying ectopic X-inactivation center sequences are also targeted to the perinucleolar compartment. Deleting Xist results in a loss of nucleolar association and an inability to maintain Xi heterochromatin, leading to Xi reactivation at the single gene level. We propose that the Xi must continuously visit the perinucleolar compartment to maintain its epigenetic state. These data raise a mechanism by which chromatin states can be replicated by spatial and temporal separation in the nucleus.
在哺乳动物雌性个体中，两条X染色体在表观遗传上被区分为活跃染色体和失活染色体，以平衡雄性和雌性之间X连锁基因的剂量。X染色体如何在同一细胞核中以不同方式维持仍不清楚。在这里，我们证明失活的X染色体（Xi）在与其同源配对后会靶向一个独特的核区室。在S期中期到后期，80%-90%的Xi与核仁接触并位于富含Snf2h的环内。携带异位X染色体失活中心序列的常染色体也靶向核仁周围区室。删除Xist会导致核仁关联丧失以及无法维持Xi异染色质，从而导致Xi在单基因水平上重新激活。我们提出，Xi必须持续进入核仁周围区室以维持其表观遗传状态。这些数据提出了一种机制，通过该机制染色质状态可以通过细胞核中的空间和时间分离来复制。
