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The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

发布日期:2014/8/9 7:08:04

期刊名称:Cell Research

期刊号:(2015) 25:80–92

通迅作者:Xichen Bao,Miguel A Esteban

作者单位:中科院广州生物医药与健康研究院

使用产品与服务:RNA-Seq

文章摘要: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 profiing and functional screening, we have identifid 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, lin cRN A-p21 associates with the H3K9 methyltransferase SETDB1 and the maintenance DNA methyltransferase DNMT1, which is facilitated by the RNA-binding protein HNRNPK. Consequently, l i n c R N A - p 2 1 preventsreprogramming 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.

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