Robert Finestra Teresa, Gribnau Joost
Department of Developmental Biology, Erasmus MC, Wytemaweg 80, Rotterdam CN 3015, The Netherlands.
Department of Developmental Biology, Erasmus MC, Wytemaweg 80, Rotterdam CN 3015, The Netherlands.
Curr Opin Cell Biol. 2017 Jun;46:54-61. doi: 10.1016/j.ceb.2017.01.007. Epub 2017 Feb 23.
To ensure X-linked gene dosage compensation between females (XX) and males (XY), one X chromosome undergoes X chromosome inactivation (XCI) in female cells. This process is tightly regulated throughout development by many different factors, with Xist as a key regulator, encoding a long non-coding RNA, involved in establishment of several layers of repressive epigenetic modifications. Several recent studies on XCI focusing on identification and characterization of Xist RNA-protein interactors, revealed new factors involved in gene silencing, genome topology and nuclear membrane attachment, amongst others. Also, new insights in higher order chromatin organization have been presented, revealing differences between the topological organization of active and inactive X chromosomes (Xa and Xi), with associated differences in gene expression. Finally, further evidence indicates that the inactive state of the Xi can be (partially) reversed, and that this X chromosome reactivation (XCR) might be associated with disease.
为确保雌性（XX）和雄性（XY）之间X连锁基因的剂量补偿，一条X染色体在雌性细胞中会发生X染色体失活（XCI）。在整个发育过程中，这一过程受到许多不同因素的严格调控，其中Xist作为关键调节因子，编码一种长链非编码RNA，参与建立多层抑制性表观遗传修饰。最近几项关于XCI的研究聚焦于Xist RNA-蛋白质相互作用分子的鉴定和表征，揭示了参与基因沉默、基因组拓扑结构和核膜附着等过程的新因子。此外，还提出了关于高阶染色质组织的新见解，揭示了活跃和失活X染色体（Xa和Xi）拓扑结构的差异，以及相关的基因表达差异。最后，进一步的证据表明，Xi的失活状态可以（部分）逆转，并且这种X染色体重新激活（XCR）可能与疾病有关。
