Sun Bryan K, Deaton Aimée M, Lee Jeannie T
Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, 02114, USA.
Mol Cell. 2006 Mar 3;21(5):617-28. doi: 10.1016/j.molcel.2006.01.028.
X chromosome inactivation (XCI) depends on a noncoding sense-antisense transcript pair, Xist and Tsix. At the onset of XCI, Xist RNA accumulates on one of two Xs, coating and silencing the chromosome in cis. The molecular basis for monoallelic Xist upregulation is not known, though evidence predominantly supports a posttranscriptional mechanism through RNA stabilization. Here, we test whether Tsix RNA destabilizes Xist RNA. Unexpectedly, we find that Xist upregulation is not based on transcript stabilization at all but is instead controlled by transcription in a sex-specific manner. Tsix directly regulates its transcription. On the future inactive X, Tsix downregulation induces a transient heterochromatic state in Xist, followed paradoxically by high-level Xist expression. A Tsix-deficient X chromosome adopts the heterochromatic state in pre-XCI cells. This state persists through XCI establishment and "reverts" to a euchromatic state during XCI maintenance. We have therefore identified chromatin marks that preempt and predict asymmetric Xist expression.
X染色体失活（XCI）依赖于一个非编码的正义-反义转录本对，即Xist和Tsix。在XCI开始时，Xist RNA在两条X染色体中的一条上积累，顺式覆盖并沉默该染色体。单等位基因Xist上调的分子基础尚不清楚，尽管证据主要支持通过RNA稳定的转录后机制。在这里，我们测试Tsix RNA是否会使Xist RNA不稳定。出乎意料的是，我们发现Xist上调根本不是基于转录本稳定，而是由性别特异性的转录控制。Tsix直接调节其转录。在未来的失活X染色体上，Tsix下调会在Xist中诱导短暂的异染色质状态，随后反常地出现高水平的Xist表达。一个Tsix缺陷的X染色体在XCI前细胞中呈现异染色质状态。这种状态在XCI建立过程中持续存在，并在XCI维持期间“恢复”为常染色质状态。因此，我们已经确定了先于并预测不对称Xist表达的染色质标记。
