NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming

Qiang Zhuang; Wenjuan Li; Christina Benda; Zhijian Huang; Tanveer Ahmed; Ping Liu; Xiangpeng Guo; David P. Ibanez; Zhiwei Luo; Meng Zhang; Mazid Md Abdul; Zhongzhou Yang; Jiayin Yang; Yinghua Huang; Hui Zhang; Dehao Huang; Jianguo Zhou; Xiaofen Zhong; Xihua Zhu; Xiuling Fu; Wenxia Fan; Yulin Liu; Yan Xu; Carl Ward; Muhammad Jadoon Khan; Shahzina Kanwal; Bushra Mirza; Micky D. Tortorella; Hung-Fat Tse; Jiayu Chen; Baoming Qin; Xichen Bao; Shaorong Gao; Andrew P. Hutchins; Miguel A. Esteban

doi:10.1038/s41556-018-0047-x

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NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming

Journal article

Peer reviewed

NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming

Qiang Zhuang, Wenjuan Li, Christina Benda, Zhijian Huang, Tanveer Ahmed, Ping Liu, Xiangpeng Guo, David P. Ibanez, Zhiwei Luo, Meng Zhang, …

Nature cell biology, Vol.20(4), pp.400-412

01/04/2018

DOI: https://doi.org/10.1038/s41556-018-0047-x

PMID: 29531310

Abstract

Cell Biology

Life Sciences & Biomedicine

Science & Technology

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.

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Title: NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming
Creators - without role: Qiang Zhuang - Guangzhou Institutes of Biomedicine and Health
Wenjuan Li - Guangzhou Institutes of Biomedicine and Health
Christina Benda - Guangzhou Institutes of Biomedicine and Health
Zhijian Huang - Guangzhou Institutes of Biomedicine and Health
Tanveer Ahmed - Guangzhou Institutes of Biomedicine and Health
Ping Liu - Guangzhou Institutes of Biomedicine and Health
Xiangpeng Guo - Guangzhou Institutes of Biomedicine and Health
David P. Ibanez - Guangzhou Institutes of Biomedicine and Health
Zhiwei Luo - Guangzhou Institutes of Biomedicine and Health
Meng Zhang - Guangzhou Institutes of Biomedicine and Health
Mazid Md Abdul - Guangzhou Institutes of Biomedicine and Health
Zhongzhou Yang - Guangzhou Institutes of Biomedicine and Health
Jiayin Yang - Chinese University of Hong Kong
Yinghua Huang - Guangzhou Institutes of Biomedicine and Health
Hui Zhang - Guangzhou Institutes of Biomedicine and Health
Dehao Huang - Guangzhou Institutes of Biomedicine and Health
Jianguo Zhou - Guangzhou Institutes of Biomedicine and Health
Xiaofen Zhong - Guangzhou Institutes of Biomedicine and Health
Xihua Zhu - Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Lab RNA Chromatin & Human Dis, Guangzhou, Guangdong, Peoples R China
Xiuling Fu - Southern Univ Sci & Technol China, Dept Biol, Shenzhen, Peoples R China
Wenxia Fan - Guangzhou Institutes of Biomedicine and Health
Yulin Liu - Beike Biotechnology
Yan Xu - Guangzhou Institutes of Biomedicine and Health
Carl Ward - Guangzhou Institutes of Biomedicine and Health
Muhammad Jadoon Khan - Guangzhou Institutes of Biomedicine and Health
Shahzina Kanwal - Guangzhou Institutes of Biomedicine and Health
Bushra Mirza - Quaid-i-Azam University
Micky D. Tortorella - Guangzhou Institutes of Biomedicine and Health
Hung-Fat Tse - Chinese University of Hong Kong
Jiayu Chen - Tongji University
Baoming Qin - Guangzhou Institutes of Biomedicine and Health
Xichen Bao - Guangzhou Institutes of Biomedicine and Health
Shaorong Gao - Tongji University
Andrew P. Hutchins - Southern University of Science and Technology
Miguel A. Esteban - Guangzhou Institutes of Biomedicine and Health
Publication Details: Nature cell biology, Vol.20(4), pp.400-412
Publisher: Springer Nature
Number of pages: 15
Grant note: 81261160506 / National Natural Science Foundation of China/Research Grants Council Joint Research Scheme; National Natural Science Foundation of China (NSFC) 2016YFA0100102; 2016YFA0100300 / National Key Research and Development Program of China XDA16030502 / Chinese Academy of Sciences CAS-TWAS President's PhD Fellowship 2017B030314056 / Science and Technology Planning Project of Guangdong Province, China 2013B050800010; 2014A030312001; 2014A030310327; 2016B030229007; 2016A050503037; 2015A030308007 / Guangdong Province Science and Technology Program CAS16HU01/CAS16902 / Chinese Academy of Sciences-Croucher Funding Scheme for Joint Laboratories 31461143011 / National Natural Science Foundation of China-Israel Science Foundation Joint Research Scheme JCYJ20150331142757383; JCYJ20170307110638890 / Shenzhen Science and Technology Council Basic Research program CAS President's International Fellowships GJHZ1242 / Queensland-Chinese Academy of Sciences (Q-CAS) project 31371513; 31471242; 81571238; 31671537; 31370995; 31571524 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) Zhujiang Talents-Overseas Young Talents Postdoctoral Fellowship 201508030027 / Guangzhou Science and Technology Program
Identifiers: 9950096508331
Academic Unit: King Saud University
Language: English
Resource Type: Journal article