Long-range cis effects of ectopic X-inactivation centres on a mouse autosome
Long-range cis effects of ectopic X-inactivation centres on a mouse autosome
复制标题
DOI：
10.1038/386275a0
复制
发表时间：
1997-03-20
期刊：
影响因子：
64.8
通讯作者：
Jaenisch, R
中科院分区：
文献类型：
--
作者：
Lee, JT;Jaenisch, R
在哺乳动物中，X染色体的独特之处在于它能够完全失活。这种X染色体失活的进化是为了补偿具有两条X染色体的雌性和具有一条X染色体的雄性之间的基因剂量差异。单个雌性X染色体的转录沉默由Xist顺式调控，其RNA产物覆盖在失活的X染色体（Xi）上，同时受X染色体失活中心（Xic）调控。一项转基因研究将Xic限定在包括Xist在内的450千碱基范围内，并证明它足以启动X染色体失活。在此我们报道，异位的Xist RNA完全覆盖转基因的12号染色体。超过50厘摩区域内基因的表达降低了两倍，并且在成纤维细胞中仅能从正常的同源染色体上检测到。此外，异位的Xic作用导致了整个染色体的变化，这些变化是Xi的特征：DNA复制延迟，组蛋白H4明显低乙酰化。我们的研究结果表明，常染色体上存在类似于X染色体失活的长距离顺式效应，这意味着Xic既能启动X染色体失活，又能驱动异染色质形成。因此，染色体范围的基因调控潜能并非X染色体DNA所固有，在具有Xic的常染色体上也可能发生。
In mammals, the X chromosome is unique in being capable of complete inactivation. Such X inactivation evolved to compensate for gene dosage differences between females with two X chromosomes and males with one(1). Transcriptional silencing of a, single female X chromosome is controlled in cis by Xist(2), whose RNA product coats the inactive X chromosome (X(i))(3), and the X-inactivation centre (Xic)(4). A transgenic study limited the Xic to 450 kilobases including Xist, and demonstrated that it is sufficient to initiate X inactivation(5). Here we report that ectopic Xist RNA completely coats transgenic chromosome 12. Expression of genes over 50 centimorgans was reduced two-fold and was detected only from the normal homologue in fibroblasts. Moreover, ectopic Xic action resulted in chromosome-wide changes that are characteristic of the X(i): DNA replication was delayed, and histone H4 was markedly hypoacetylated. Our findings suggest long-range cis effects on the autosome similar to those of X inactivation, and imply that the Xic can both initiate X inactivation and drive heterochromatin formation, Thus, the potential for chromosome-wide gene regulation is not intrinsic to X-chromosome DNA, but can also occur on autosomes possessing the Xic.