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

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; Jonathan Frampton; Hung-Fat Tse; Duanqing Pei; Huating Wang; Biliang Zhang; Miguel A Esteban

doi:10.1038/cr.2014.165

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

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, Jonathan Frampton, Hung-Fat Tse, Duanqing Pei, Huating Wang, Biliang ZhangMiguel A Esteban

Cancer and Genomic Sciences

Research output: Contribution to journal › Article › peer-review

120 Citations (Scopus)

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.

Original language	English
Pages (from-to)	80-92
Number of pages	13
Journal	Cell Research
Volume	25
Issue number	1
Early online date	16 Dec 2014
DOIs	https://doi.org/10.1038/cr.2014.165
Publication status	Published - 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

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10.1038/cr.2014.165Licence: None: All rights reserved

Developing Stem Cell Therapies for the Treatment of Inherited and Acquired Liver Disease
Frampton, J. (Principal Investigator) & Newsome, P. (Co-Investigator)
Medical Research Council
3/12/12 → 30/09/13
Project: Research Councils

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Bao, X., Wu, H., Zhu, X., Guo, X., Hutchins, A. P., Luo, Z., Song, H., Chen, Y., Lai, K., Yin, M., Xu, L., Zhou, L., Chen, J., Wang, D., Qin, B., Frampton, J., Tse, H.-F., Pei, D., Wang, H., ... Esteban, M. A. (2015). The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters. Cell Research, 25(1), 80-92. https://doi.org/10.1038/cr.2014.165

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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.",

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",

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

year = "2015",

month = jan,

doi = "10.1038/cr.2014.165",

language = "English",

volume = "25",

pages = "80--92",

journal = "Cell Research",

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Bao, X, Wu, H, Zhu, X, Guo, X, Hutchins, AP, Luo, Z, Song, H, Chen, Y, Lai, K, Yin, M, Xu, L, Zhou, L, Chen, J, Wang, D, Qin, B, Frampton, J, Tse, H-F, Pei, D, Wang, H, Zhang, B & Esteban, MA 2015, 'The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters', Cell Research, vol. 25, no. 1, pp. 80-92. https://doi.org/10.1038/cr.2014.165

TY - JOUR

T1 - The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

AU - Bao, Xichen

AU - Wu, Haitao

AU - Zhu, Xihua

AU - Guo, Xiangpeng

AU - Hutchins, Andrew P

AU - Luo, Zhiwei

AU - Song, Hong

AU - Chen, Yongqiang

AU - Lai, Keyu

AU - Yin, Menghui

AU - Xu, Lingxiao

AU - Zhou, Liang

AU - Chen, Jiekai

AU - Wang, Dongye

AU - Qin, Baoming

AU - Frampton, Jonathan

AU - Tse, Hung-Fat

AU - Pei, Duanqing

AU - Wang, Huating

AU - Zhang, Biliang

AU - Esteban, Miguel A

PY - 2015/1

Y1 - 2015/1

N2 - 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.

AB - 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.

KW - Animals

KW - Apoptosis

KW - Cell Proliferation

KW - Cellular Reprogramming

KW - CpG Islands

KW - DNA (Cytosine-5-)-Methyltransferase

KW - DNA Methylation

KW - Heterochromatin

KW - Histone-Lysine N-Methyltransferase

KW - Histones

KW - Induced Pluripotent Stem Cells

KW - Mice

KW - Promoter Regions, Genetic

KW - RNA, Long Noncoding

KW - Tumor Suppressor Protein p53

U2 - 10.1038/cr.2014.165

DO - 10.1038/cr.2014.165

M3 - Article

C2 - 25512341

SN - 1001-0602

VL - 25

SP - 80

EP - 92

JO - Cell Research

JF - Cell Research

IS - 1

ER -

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

Abstract

Keywords

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Projects

Developing Stem Cell Therapies for the Treatment of Inherited and Acquired Liver Disease

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