Lührig Sandra, Siamishi Iliana, Tesmer-Wolf Marieke, Zechner Ulrich, Engel Wolfgang, Nolte Jessica
1 Institute of Human Genetics, University of Göttingen , Göttingen, Germany .
Stem Cells Dev. 2014 Dec 1;23(23):2862-74. doi: 10.1089/scd.2013.0470. Epub 2014 Aug 5.
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.
基因Lrrc34(富含亮氨酸重复序列34)在多能干细胞中高度表达,且其表达在分化时会强烈下调。这些结果使我们推测Lrrc34在多能性的调控和维持中发挥作用。表达分析表明,Lrrc34主要在多能干细胞中表达,并对已知的多能性基因如Oct4的表达有影响。Lrrc34启动子的甲基化研究显示,未分化干细胞中存在低甲基化,组蛋白修饰的染色质免疫沉淀-定量聚合酶链反应分析表明,Lrrc34启动子区域存在富集的激活组蛋白修饰。此外,我们能够证实核仁——核糖体生物合成的场所——是LRRC34蛋白的主要亚细胞定位。我们通过两种独立方法验证了LRRC34与两种主要核仁蛋白核磷蛋白和核仁素的相互作用,这表明Lrrc34在多能干细胞的核糖体生物合成中发挥作用。总之,LRRC34是一种主要在多能干细胞中表达的新型核仁蛋白。其表达改变对多能性调控基因有影响,并且它与已知参与核糖体生物合成的蛋白相互作用。因此,我们推测Lrrc34在多能干细胞的核糖体生物合成中发挥作用。