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

Research output: Contribution to journalArticle

Authors

  • Xichen Bao
  • Haitao Wu
  • Xihua Zhu
  • Xiangpeng Guo
  • Andrew P Hutchins
  • Zhiwei Luo
  • Hong Song
  • Yongqiang Chen
  • Keyu Lai
  • Menghui Yin
  • Lingxiao Xu
  • Liang Zhou
  • Jiekai Chen
  • Dongye Wang
  • Baoming Qin
  • Hung-Fat Tse
  • Duanqing Pei
  • Huating Wang
  • Biliang Zhang
  • Miguel A Esteban

Colleges, School and Institutes

Abstract

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.

Details

Original languageEnglish
Pages (from-to)80-92
Number of pages13
JournalCell Research
Volume25
Issue number1
Early online date16 Dec 2014
Publication statusPublished - Jan 2015

Keywords

  • Animals, Apoptosis, Cell Proliferation, Cellular Reprogramming, CpG Islands, DNA (Cytosine-5-)-Methyltransferase, DNA Methylation, Heterochromatin, Histone-Lysine N-Methyltransferase, Histones, Induced Pluripotent Stem Cells, Mice, Promoter Regions, Genetic, RNA, Long Noncoding, Tumor Suppressor Protein p53