The Matrix Protein hnRNP U Is Required for Chromosomal Localization of Xist RNA
The Matrix Protein hnRNP U Is Required for Chromosomal Localization of Xist RNA
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DOI：
10.1016/j.devcel.2010.08.006
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发表时间：
2010-09-14
影响因子：
11.8
通讯作者：
Nakagawa, Shinichi
中科院分区：
文献类型：
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作者：
Hasegawa, Yuko;Brockdorff, Neil;Nakagawa, Shinichi
在XX型雌性哺乳动物中，两条X染色体中的一条会发生表观遗传失活，以使基因表达与XY型雄性相等。失活X染色体（Xi）的形成受X连锁的长链非编码RNA Xist调控，Xist在染色体上顺式积累于整条染色体并诱导异染色质形成。然而，Xist RNA“涂抹”Xi的机制长期以来一直不清楚。在此，我们表明一种基质蛋白hnRNP U/SP120/SAF - A是Xist RNA在Xi上积累所必需的。Xist RNA与hnRNP U相互作用，并且在hnRNP U缺失时，Xist RNA从Xi上脱离并弥散地定位于核质中。此外，缺乏hnRNP U表达的胚胎干细胞无法形成Xi。我们提出，与基质蛋白的结合是Xist RNA对基因表达进行表观遗传调控的关键步骤。
In XX female mammals, one of the two X chromosomes is epigenetically inactivated to equalize gene expression with XY males. The formation of the inactive X chromosome (Xi) is regulated by an X-linked long noncoding RNA Xist, which accumulates on the entire length of the chromosome in cis and induces heterochromatin formation. However, the mechanism by which Xist RNA "paints" the Xi has long remained elusive. Here, we show that a matrix protein hnRNP U/SP120/SAF-A is required for the accumulation of Xist RNA on the Xi. Xist RNA and hnRNP U interact and upon depletion of hnRNP U, Xist RNA is detached from the Xi and diffusely localized into the nucleoplasm. In addition, ES cells lacking hnRNP U expression fail to form the Xi. We propose that the association with matrix proteins is an essential step in the epigenetic regulation of gene expression by Xist RNA.