UMR 7216 Epigénétique et Destin Cellulaire, CNRS/Université Paris-Diderot Paris 7, 35 rue Hélène Brion, 75205 Paris, France.
Biochimie. 2011 Nov;93(11):1935-42. doi: 10.1016/j.biochi.2011.07.009. Epub 2011 Jul 27.
Random X chromosome inactivation (XCI), the eutherian mechanism of X-linked gene dosage compensation, is controlled by a cis-acting locus termed the X-inactivation center (Xic). One of the striking features that characterize the Xic landscape is the abundance of loci transcribing non-coding RNAs (ncRNAs), including Xist, the master regulator of the inactivation process. Recent comparative genomic analyses have depicted the evolutionary scenario behind the origin of the X-inactivation center, revealing that this locus evolved from a region harboring protein-coding genes. During mammalian radiation, this ancestral protein-coding region was disrupted in the marsupial group, whilst it provided in eutherian lineage the starting material for the non-translated RNAs of the X-inactivation center. The emergence of non-coding genes occurred by a dual mechanism involving loss of protein-coding function of the pre-existing genes and integration of different classes of mobile elements, some of which modeled the structure and sequence of the non-coding genes in a species-specific manner. The rising genes started to produce transcripts that acquired function in regulating the epigenetic status of the X chromosome, as shown for Xist, its antisense Tsix, Jpx, and recently suggested for Ftx. Thus, the appearance of the Xic, which occurred after the divergence between eutherians and marsupials, was the basis for the evolution of random X inactivation as a strategy to achieve dosage compensation.
随机 X 染色体失活（XCI）是哺乳动物 X 连锁基因剂量补偿的机制，受顺式作用位点 X 失活中心（Xic）控制。Xic 景观的一个显著特征是大量转录非编码 RNA（ncRNA）的基因，包括 Xist，它是失活过程的主要调节剂。最近的比较基因组分析描绘了 X 失活中心起源背后的进化情景，揭示了这个位点是从一个含有蛋白编码基因的区域进化而来的。在哺乳动物辐射过程中，这个祖先的蛋白编码区域在有袋动物群中被破坏，而在真兽类中，它为 X 失活中心的非翻译 RNA 提供了起始材料。非编码基因的出现是通过双重机制发生的，涉及到预先存在的基因的蛋白编码功能的丧失和不同类别的移动元件的整合，其中一些以物种特异性的方式模拟了非编码基因的结构和序列。新兴的基因开始产生转录本，这些转录本获得了调节 X 染色体表观遗传状态的功能，正如 Xist、其反义 Tsix、Jpx 所证明的那样，最近也被认为是 Ftx。因此，Xic 的出现是在真兽类和有袋类分化之后发生的，它是随机 X 失活作为一种实现剂量补偿策略的进化基础。
