title: The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters.
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.
authors.affiliation: 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.
authors.forename: Xichen
authors.initials: X
authors.lastname: Bao
authors.affiliation: 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.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Xihua
authors.initials: X
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Xiangpeng
authors.initials: X
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Hutchins
authors.affiliation: 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.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Keyu
authors.initials: K
authors.lastname: Lai
authors.affiliation: Laboratory of RNA Chemical Biology, State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China.
authors.forename: Menghui
authors.initials: M
authors.lastname: Yin
authors.affiliation: School of Life Sciences, Shandong University, Jinan, Shandong 250100, China.
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Radiation Medicine, School of Public Health and Tropic Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Jiekai
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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] Drug Discovery Pipeline Group, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China.
authors.forename: Dongye
authors.initials: D
authors.lastname: Wang
authors.affiliation: 1] 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 [2] Laboratory of Metabolism and Cell Fate, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China [3] Hong 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.
authors.forename: Baoming
authors.initials: B
authors.lastname: Qin
authors.affiliation: School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Frampton
authors.affiliation: 1] Hong 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 [2] Cardiology Division, Department of medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China [3] Shenzhen Institutes of Research and Innovation, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.affiliation: 1] 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 [2] Hong 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.
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
authors.affiliation: Li Ka Shing Institute of Health Sciences, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Huating
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of RNA Chemical Biology, State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China.
authors.forename: Biliang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: 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] Hong 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.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Esteban
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D065150:Cellular Reprogramming; D018899:CpG Islands; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D006570:Heterochromatin; D006657:Histones; D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; C516239:SETDB1 protein, mouse