Sensing X chromosome pairs before X inactivation via a novel X-pairing region of the Xic
Sensing X chromosome pairs before X inactivation via a novel X-pairing region of the Xic
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DOI：
10.1126/science.1149420
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发表时间：
2007-12-07
期刊：
影响因子：
56.9
通讯作者：
Heard, E.
中科院分区：
文献类型：
--
作者：
Augui, S.;Filion, G. J.;Heard, E.
哺乳动物的剂量补偿涉及女性两条X染色体之一的沉默，并由X失活中心（Xic）控制。Xic包括Xist及其反义转录单位Tsix/Xite，以某种方式感知X染色体的数量，并触发女性两条X染色体之一的Xist上调。我们发现，位于Xist上游数百个Xic酶的小鼠Xic片段在X失活开始之前将两个Xic结合在一起。该区域甚至可以作为异位单拷贝转基因自主驱动Xic反式相互作用。它引入男性胚胎干细胞是强烈选择反对，与反式激活Xist的可能作用一致。我们提出，这种新的X配对区域（XPR）的XIC驱动的同源协会使细胞能够感知到一个以上的X染色体存在，并协调相互Xist/Tsix表达。
Mammalian dosage compensation involves silencing of one of the two X chromosomes in females and is controlled by the X-inactivation center (Xic). The Xic, which includes Xist and its antisense transcription unit Tsix/Xite, somehow senses the number of X chromosomes and triggers Xist up-regulation from one of the two X chromosomes in females. We found that a segment of the mouse Xic lying several hundred kilobases upstream of Xist brings the two Xics together before the onset of X inactivation. This region can autonomously drive Xic trans-interactions even as an ectopic single-copy transgene. Its introduction into male embryonic stem cells is strongly selected against, consistent with a possible role in trans-activating Xist. We propose that homologous associations driven by this novel X-pairing region (Xpr) of the Xic enable a cell to sense that more than one X chromosome is present and coordinate reciprocal Xist/Tsix expression.