Xite, X-inactivation Intergenic transcription elements that regulate the probability of choice
Xite, X-inactivation Intergenic transcription elements that regulate the probability of choice
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DOI：
10.1016/s1097-2765(03)00063-7
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发表时间：
2003-03-01
期刊：
影响因子：
16
通讯作者：
Lee, JT
中科院分区：
文献类型：
--
作者：
Ogawa, Y;Lee, JT
等位基因表达差异导致表型变异。在X染色体失活（XCI）中，不利的XCI比例促进X连锁疾病在女性中的外显率。在XCI期间，一个X被Xist随机沉默。X染色体的选择是由Tsix的不对称表达决定的，Tsix的反义作用抑制Xist。在这里，我们发现了一个顺式元件在小鼠x失活中心调节Tsix。希特有基因间转录起始位点和DNasel超敏位点，存在等位基因差异。在XCI开始时，删除Xite会下调顺式t6，并使XCI比例偏斜，这表明Xite促进了t6在活性x上的持久性，截断Xite RNA是无关紧要的，表明Xite的作用不需要完整的转录本。我们提出等位基因特异性Xite作用促进t6不对称并产生X染色体不平等。因此，Xite是Xce的候选者，Xce是XCI比率的经典修饰符。
Allelic expression differences contribute to phenotypic variation. In X chromosome inactivation (XCI), unfavorable XCI ratios promote X-linked disease penetrance in females. During XCI, one X is randomly silenced by Xist. X chromosome choice is determined by asymmetric expression of Tsix whose antisense action represses Xist. Here, we discover a cis element in the mouse X-inactivation center that regulates Tsix. Xite harbors intergenic transcription start sites and DNasel hypersensitive sites with allelic differences. At the onset of XCI, deleting Xite downregulates Tsix in cis and skews XCI ratios, suggesting that Xite promotes Tsix persistence on the active X. Truncating Xite RNA is inconsequential, indicating that Xite action does not require intact transcripts. We propose that allele-specific Xite action promotes Tsix asymmetry and generates X chromosome inequality. Therefore, Xite is a candidate for the Xce, the classical modifier of XCI ratios.