Lrrc34, a novel nucleolar protein, interacts with npm1 and ncl and has an impact on pluripotent stem cells.
Lrrc34, a novel nucleolar protein, interacts with npm1 and ncl and has an impact on pluripotent stem cells.
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DOI：
10.1089/scd.2013.0470
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发表时间：
2014-07
影响因子：
4
通讯作者：
Sandra Lührig;Iliana Siamishi;Marieke Tesmer-Wolf;U. Zechner;W. Engel;J. Nolte
中科院分区：
文献类型：
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作者：
Sandra Lührig;Iliana Siamishi;Marieke Tesmer-Wolf;U. Zechner;W. Engel;J. Nolte
基因Lrrc 34（富含亮氨酸重复序列的34）在多能干细胞中高度表达，并且其表达在分化时强烈下调。这些结果让我们提出Lrrc 34在调节和维持多能性中的作用。表达分析显示，Lrrc 34主要在多能干细胞中表达，并对已知多能性基因（如Oct 4）的表达产生影响。Lrrc 34启动子的甲基化研究表明，在未分化的干细胞和染色质免疫沉淀-定量聚合酶链反应分析组蛋白修饰低甲基化揭示了丰富的激活组蛋白修饰Lrrc 34启动子区域。此外，我们可以验证核仁的地方核糖体生物合成的主要亚细胞定位的LRRC 34蛋白。我们已经通过两种独立的方法验证了LRRC 34与两种主要核仁蛋白Nucleophosmin和Nucleolin的相互作用，表明LRRC 34在多能干细胞的核糖体生物发生中的作用。总之，LRRC 34是一种新的核仁蛋白，主要在多能干细胞中表达。其改变的表达对多能性调节基因具有影响，并且其与已知参与核糖体生物发生的蛋白质相互作用。因此，我们提出了Lrrc 34在多能干细胞的核糖体生物合成中的作用。
The gene Lrrc34 (leucine rich repeat containing 34) is highly expressed in pluripotent stem cells and its expression is strongly downregulated upon differentiation. These results let us to suggest a role for Lrrc34 in the regulation and maintenance of pluripotency. Expression analyses revealed that Lrrc34 is predominantly expressed in pluripotent stem cells and has an impact on the expression of known pluripotency genes, such as Oct4. Methylation studies of the Lrrc34 promoter showed a hypomethylation in undifferentiated stem cells and chromatin immunoprecipitation-quantitative polymerase chain reaction analyses of histone modifications revealed an enrichment of activating histone modifications on the Lrrc34 promoter region. Further, we could verify the nucleolus-the place of ribosome biogenesis-as the major subcellular localization of the LRRC34 protein. We have verified the interaction of LRRC34 with two major nucleolar proteins, Nucleophosmin and Nucleolin, by two independent methods, suggesting a role for Lrrc34 in ribosome biogenesis of pluripotent stem cells. In conclusion, LRRC34 is a novel nucleolar protein that is predominantly expressed in pluripotent stem cells. Its altered expression has an impact on pluripotency-regulating genes and it interacts with proteins known to be involved in ribosome biogenesis. Therefore we suggest a role for Lrrc34 in ribosome biogenesis of pluripotent stem cells.