Volume 25, No 1, Jan 2015
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 25 Issue 1, January 2015: 80-92
ORIGINAL ARTICLES
The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters
Xichen Bao1,2,*, Haitao Wu1,2,3,*, Xihua Zhu1,2,3,*, Xiangpeng Guo1,2, Andrew P Hutchins2, Zhiwei Luo1,2, Hong Song2, Yongqiang Chen2, Keyu Lai2, Menghui Yin4, Lingxiao Xu5, Liang Zhou6, Jiekai Chen2, Dongye Wang1,2,7, Baoming Qin2,8,9, Jon Frampton10, Hung-Fat Tse9,11,12, Duanqing Pei2,9, Huating Wang13, Biliang Zhang4 and Miguel A Esteban1,2,9
1Laboratory of Chromatin and Human Disease, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China
2Key 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
3University of Chinese Academy of Sciences, Beijing 100049, China
4Laboratory of RNA Chemical Biology, State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China
5School of Life Sciences, Shandong University, Jinan, Shandong 250100, China
6Department of Radiation Medicine, School of Public Health and Tropic Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China
7Drug Discovery Pipeline Group, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China
8Laboratory of Metabolism and Cell Fate, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China
9Hong Kong - Guangdong Joint Laboratory of Stem Cells and Regenerative Medicine, the University of Hong Kong and Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China
10School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK
11Cardiology Division, Department of medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China
12Shenzhen Institutes of Research and Innovation, The University of Hong Kong, Hong Kong SAR, China
13Li Ka Shing Institute of Health Sciences, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
Correspondence: Xichen Bao, Tel: +86-20-3229-0481; Fax: +86-20-3206-8110 E-mail: bao_xichen@gibh.ac.cn; Miguel A Esteban, Tel: +86-20-3202-2920; Fax: +86-20-3206-8110(miguel@gibh.ac.cn)
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.
10.1038/cr.2014.165
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