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NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming.
Zhuang, Qiang; Li, Wenjuan; Benda, Christina; Huang, Zhijian; Ahmed, Tanveer; Liu, Ping; Guo, Xiangpeng; Ibañez, David P; Luo, Zhiwei; Zhang, Meng; Abdul, Mazid Md; Yang, Zhongzhou; Yang, Jiayin; Huang, Yinghua; Zhang, Hui; Huang, Dehao; Zhou, Jianguo; Zhong, Xiaofen; Zhu, Xihua; Fu, Xiuling; Fan, Wenxia; Liu, Yulin; Xu, Yan; Ward, Carl; Khan, Muhammad Jadoon; Kanwal, Shahzina; Mirza, Bushra; Tortorella, Micky D; Tse, Hung-Fat; Chen, Jiayu; Qin, Baoming; Bao, Xichen; Gao, Shaorong; Hutchins, Andrew P; Esteban, Miguel A.
Affiliation
  • Zhuang Q; Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Joint School of Life Sciences, Guangzhou Medical University and Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Li W; Laboratory of RNA, Chromatin, and Human Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Benda C; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Huang Z; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China.
  • Ahmed T; Laboratory of RNA, Chromatin, and Human Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Liu P; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Guo X; University of Chinese Academy of Sciences, Beijing, China.
  • Ibañez DP; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China.
  • Luo Z; Laboratory of RNA, Chromatin, and Human Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Zhang M; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Abdul MM; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China.
  • Yang Z; Laboratory of RNA, Chromatin, and Human Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Yang J; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Huang Y; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China.
  • Zhang H; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Huang D; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China.
  • Zhou J; Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.
  • Zhong X; Laboratory of Metabolism and Cell Fate, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Zhu X; Laboratory of RNA, Chromatin, and Human Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Fu X; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Fan W; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China.
  • Liu Y; Institute of Health Sciences, Anhui University, Hefei, China.
  • Xu Y; Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Joint School of Life Sciences, Guangzhou Medical University and Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Ward C; Laboratory of RNA, Chromatin, and Human Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Khan MJ; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Kanwal S; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China.
  • Mirza B; Laboratory of RNA, Chromatin, and Human Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Tortorella MD; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Tse HF; University of Chinese Academy of Sciences, Beijing, China.
  • Chen J; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China.
  • Qin B; Laboratory of RNA, Chromatin, and Human Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Bao X; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Gao S; University of Chinese Academy of Sciences, Beijing, China.
  • Hutchins AP; Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China.
  • Esteban MA; Laboratory of RNA, Chromatin, and Human Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Nat Cell Biol ; 20(4): 400-412, 2018 04.
Article in En | MEDLINE | ID: mdl-29531310
ABSTRACT
Somatic cell reprogramming by exogenous factors requires cooperation with transcriptional co-activators and co-repressors to effectively remodel the epigenetic environment. How this interplay is regulated remains poorly understood. Here, we demonstrate that NCoR/SMRT co-repressors bind to pluripotency loci to create a barrier to reprogramming with the four Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC), and consequently, suppressing NCoR/SMRT significantly enhances reprogramming efficiency and kinetics. The core epigenetic subunit of the NCoR/SMRT complex, histone deacetylase 3 (HDAC3), contributes to the effects of NCoR/SMRT by inducing histone deacetylation at pluripotency loci. Among the Yamanaka factors, recruitment of NCoR/SMRT-HDAC3 to genomic loci is mostly facilitated by c-MYC. Hence, we describe how c-MYC is beneficial for the early phase of reprogramming but deleterious later. Overall, we uncover a role for NCoR/SMRT co-repressors in reprogramming and propose a dual function for c-MYC in this process.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proto-Oncogene Proteins c-myc / Pluripotent Stem Cells / Epigenesis, Genetic / Cellular Reprogramming / Nuclear Receptor Co-Repressor 1 / Nuclear Receptor Co-Repressor 2 / Mouse Embryonic Stem Cells Limits: Animals / Humans Language: En Journal: Nat Cell Biol Year: 2018 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proto-Oncogene Proteins c-myc / Pluripotent Stem Cells / Epigenesis, Genetic / Cellular Reprogramming / Nuclear Receptor Co-Repressor 1 / Nuclear Receptor Co-Repressor 2 / Mouse Embryonic Stem Cells Limits: Animals / Humans Language: En Journal: Nat Cell Biol Year: 2018 Document type: Article Affiliation country: