The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory.
The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory.
复制标题
DOI：
10.1101/gad.295907.117
复制
发表时间：
2017-05-01
影响因子：
10.5
通讯作者：
Coverley D
中科院分区：
文献类型：
--
作者：
Ridings-Figueroa R;Stewart ER;Nesterova TB;Coker H;Pintacuda G;Godwin J;Wilson R;Haslam A;Lilley F;Ruigrok R;Bageghni SA;Albadrani G;Mansfield W;Roulson JA;Brockdorff N;Ainscough JFX;Coverley D
Ridings-Figueroa等人发现，核基质蛋白Cip 1相互作用锌指蛋白1（CIZ 1）在小鼠和人类雌性细胞中高度富集在无活性X染色体（Xi）上，并通过与RNA依赖性核基质相互作用而保留。他们的研究结果表明，CIZ 1在将Xist锚定到特定体细胞谱系的核基质中起着至关重要的作用。核基质蛋白Cip 1相互作用锌指蛋白1（CIZ 1）促进与细胞周期蛋白相关的DNA复制，并与成人和儿童癌症有关。在这里，我们表明CIZ 1在小鼠和人类女性细胞中高度富集在非活性X染色体（Xi）上，并通过与RNA依赖性核基质的相互作用而保留。CIZ 1在胚胎干细胞中X失活的最早阶段响应于X失活特异性转录物（Xist）RNA的表达而被募集到Xi，并且依赖于CIZ 1的C末端核基质锚结构域和Xist的E重复序列。CIZ 1-null小鼠，虽然可行，显示完全渗透女性特异性淋巴增生性疾病。有趣的是，在来自CIZ 1缺失胚胎的小鼠胚胎成纤维细胞中，Xist RNA定位被破坏，高度分散在核质中而不是焦点。在CIZ 1的重新表达后，局灶性定位恢复。Xist RNA的局灶性定位也在从CIZ 1缺失动物分离的活化B和T细胞中被破坏，这表明了对女性特异性淋巴组织增生性疾病的可能解释。总之，这些发现表明CIZ 1在将Xist锚定到特定体细胞谱系的核基质中具有重要作用。
Here, Ridings-Figueroa et al. show that the nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells and is retained by interaction with the RNA-dependent nuclear matrix. Their findings suggest that CIZ1 has an essential role in anchoring Xist to the nuclear matrix in specific somatic lineages. The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells and is retained by interaction with the RNA-dependent nuclear matrix. CIZ1 is recruited to Xi in response to expression of X inactive-specific transcript (Xist) RNA during the earliest stages of X inactivation in embryonic stem cells and is dependent on the C-terminal nuclear matrix anchor domain of CIZ1 and the E repeats of Xist. CIZ1-null mice, although viable, display fully penetrant female-specific lymphoproliferative disorder. Interestingly, in mouse embryonic fibroblast cells derived from CIZ1-null embryos, Xist RNA localization is disrupted, being highly dispersed through the nucleoplasm rather than focal. Focal localization is reinstated following re-expression of CIZ1. Focal localization of Xist RNA is also disrupted in activated B and T cells isolated from CIZ1-null animals, suggesting a possible explanation for female-specific lymphoproliferative disorder. Together, these findings suggest that CIZ1 has an essential role in anchoring Xist to the nuclear matrix in specific somatic lineages.