p53 诱导的长链非编码 RNA-p21 通过维持多能性基因启动子处的 H3K9me3 和 CpG 甲基化来破坏体细胞重编程。
The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters.
作者信息
Bao Xichen, Wu Haitao, Zhu Xihua, Guo Xiangpeng, Hutchins Andrew P, Luo Zhiwei, Song Hong, Chen Yongqiang, Lai Keyu, Yin Menghui, Xu Lingxiao, Zhou Liang, Chen Jiekai, Wang Dongye, Qin Baoming, Frampton Jon, Tse Hung-Fat, Pei Duanqing, Wang Huating, Zhang Biliang, Esteban Miguel A
机构信息
1] Laboratory of Chromatin and Human Disease, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China [2] Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China.
1] Laboratory of Chromatin and Human Disease, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China [2] Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China [3] University of Chinese Academy of Sciences, Beijing 100049, China.
出版信息
Cell Res. 2015 Jan;25(1):80-92. doi: 10.1038/cr.2014.165. Epub 2014 Dec 16.
Recent studies have boosted our understanding of long noncoding RNAs (lncRNAs) in numerous biological processes, but few have examined their roles in somatic cell reprogramming. Through expression profiling and functional screening, we have identified that the large intergenic noncoding RNA p21 (lincRNA-p21) impairs reprogramming. Notably, lincRNA-p21 is induced by p53 but does not promote apoptosis or cell senescence in reprogramming. Instead, lincRNA-p21 associates with the H3K9 methyltransferase SETDB1 and the maintenance DNA methyltransferase DNMT1, which is facilitated by the RNA-binding protein HNRNPK. Consequently, lincRNA-p21 prevents reprogramming by sustaining H3K9me3 and/or CpG methylation at pluripotency gene promoters. Our results provide insight into the role of lncRNAs in reprogramming and establish a novel link between p53 and heterochromatin regulation.
最近的研究增进了我们对长链非编码RNA（lncRNA）在众多生物学过程中的理解，但很少有研究探讨它们在体细胞重编程中的作用。通过表达谱分析和功能筛选，我们发现大的基因间非编码RNA p21（lincRNA-p21）会损害重编程。值得注意的是，lincRNA-p21由p53诱导，但在重编程过程中不促进细胞凋亡或细胞衰老。相反，lincRNA-p21与H3K9甲基转移酶SETDB1和维持性DNA甲基转移酶DNMT1结合，这一过程由RNA结合蛋白HNRNPK促进。因此，lincRNA-p21通过维持多能性基因启动子处的H3K9me3和/或CpG甲基化来阻止重编程。我们的结果为lncRNA在重编程中的作用提供了见解，并在p53与异染色质调控之间建立了新的联系。
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