Tsix defective in splicing is competent to establish Xist silencing
Tsix defective in splicing is competent to establish Xist silencing
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DOI：
10.1242/dev.02670
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发表时间：
2006-12-15
期刊：
影响因子：
4.6
通讯作者：
Sasaki, Hiroyuki
中科院分区：
文献类型：
--
作者：
Sado, Takashi;Hoki, Yuko;Sasaki, Hiroyuki
雄性和雌性哺乳动物之间X连锁基因的剂量差异通过一种称为X失活的机制来补偿，而非编码的Xist基因在这一过程中发挥着关键作用。Xist在顺式基因中的表达受其非编码反义基因tSix的调控，其转录本(尽管其中一小部分保持未剪接)像常见的蛋白质编码RNA一样被处理。已有研究表明，某些类型的正义-反义RNA对不仅与基因调控有关，而且与各种生物体的高阶染色质结构有关。事实上，最近的研究表明，TSix通过Modi调控Xist的表达。染色质结构的阳离子。然而，目前还不清楚RNA产物对TSix的功能是否重要，或者反义转录是否足够。为了深入了解这个问题，我们在小鼠中消除了TSix的剪接产物，并探索了这种消除对TSix介导的Xist沉默的影响。令我们惊讶的是，Xist基因座稳定地被抑制在携带剪接缺陷t6等位基因的X上。此外，在Xist基因座上还正确地建立了抑制染色质构型。这些意想不到的结果表明，剪接产物对于tSix介导的Xist沉默是必不可少的。
Dosage differences of X-linked genes between male and female mammals are compensated for by a mechanism known as X-inactivation, and the noncoding Xist gene plays a crucial role in this process. The expression of Xist is regulated in cis by its noncoding antisense gene, Tsix, whose transcripts (though a fraction of them stay unspliced), are processed like common protein-coding RNAs. It has been suggested that certain classes of sense-antisense pairs of RNA are causally involved in not only gene regulation but also higher order chromatin structure in various organisms. In fact, recent studies demonstrated that Tsix modulates Xist expression through modi. cation of the chromatin structure. It is still unknown, however, whether the RNA product is important for the function of Tsix or whether the antisense transcription is sufficient. To obtain insight into this issue, we eliminated the splicing products of Tsix in the mouse and explored the effects of this elimination on Tsix-mediated Xist silencing. To our surprise, the Xist locus was stably repressed on the X carrying the splicing-defective Tsix allele. Moreover, the repressive chromatin configuration was properly established at the Xist locus. These unexpected results indicate that the splicing products are dispensable for Tsix-mediated Xist silencing.