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

Zhuang, Qiang1,2,3,4,6; Li, Wenjuan3,4,5,6; Benda, Christina3,4,6; Huang, Zhijian3,4,6; Ahmed, Tanveer4,6,7,8; Liu, Ping3,4,6,9; Guo, Xiangpeng1,2,3,4,6; Ibanez, David P.3,4,5,6; Luo, Zhiwei3,4,5,6; Zhang, Meng3,4,5,6; Abdul, Mazid Md.3,4,5,6; Yang, Zhongzhou4; Yang, Jiayin10; Huang, Yinghua1,2,4,6,8; Zhang, Hui4,6,8; Huang, Dehao3,4,5; Zhou, Jianguo3,4,6; Zhong, Xiaofen3,4; Zhu, Xihua3,4,6; Fu, Xiuling11; Fan, Wenxia3,4,6; Liu, Yulin12; Xu, Yan3,4,6; Ward, Carl3,4,6; Khan, Muhammad Jadoon3,4,6; Kanwal, Shahzina3,4,6; Mirza, Bushra7; Tortorella, Micky D.13; Tse, Hung-Fat10,14,15,16; Chen, Jiayu17; Qin, Baoming1,2,4,6,8,14,15; Bao, Xichen1,2,3,4,6; Gao, Shaorong17; Hutchins, Andrew P.11; Esteban, Miguel A.1,2,3,4,6,14,15

2018-04

10.1038/s41556-018-0047-x

NATURE CELL BIOLOGY   影响因子和分区

1465-7392

1476-4679

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.

SCI

英语

NI期刊

通讯

Science and Technology Planning Project of Guangdong Province, China[2017B030314056]

Cell Biology

Cell Biology

WOS:000428781900010

NATURE PUBLISHING GROUP

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Guangzhou Med Univ, Joint Sch Life Sci, Chinese Acad Sci, Key Lab Regenerat Biol, Guangzhou, Guangdong, Peoples R China
2.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou, Guangdong, Peoples R China
3.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Lab RNA Chromatin & Human Dis, Guangzhou, Guangdong, Peoples R China
4.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cell & Regenerat Med, Guangzhou, Guangdong, Peoples R China
5.Univ Chinese Acad Sci, Beijing, Peoples R China
6.Guangzhou Regenerat Med & Hlth Guangdong Lab GRMH, Guangzhou, Guangdong, Peoples R China
7.Quaid I Azam Univ, Dept Biochem, Islamabad, Pakistan
8.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Lab Metab & Cell Fate, Guangzhou, Guangdong, Peoples R China
9.Anhui Univ, Inst Hlth Sci, Hefei, Anhui, Peoples R China
10.Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China
11.Southern Univ Sci & Technol China, Dept Biol, Shenzhen, Peoples R China
12.Guangzhou FitGene Biotechnol Co Ltd, Guangzhou, Guangdong, Peoples R China
13.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Drug Discovery Pipeline, Guangzhou, Guangdong, Peoples R China
14.Univ Hong Kong, Hong Kong Guangdong Joint Lab Stem Cells & Regene, Hong Kong, Hong Kong, Peoples R China
15.Guangzhou Inst Biomed & Hlth, Hong Kong, Hong Kong, Peoples R China
16.Univ Hong Kong, Shenzhen Inst Res & Innovat, Hong Kong, Hong Kong, Peoples R China
17.Tongji Univ, Sch Life Sci & Technol, Shanghai, Peoples R China

Zhuang, Qiang,Li, Wenjuan,Benda, Christina,et al. NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming[J]. NATURE CELL BIOLOGY,2018,20(4):400-+.

Zhuang, Qiang.,Li, Wenjuan.,Benda, Christina.,Huang, Zhijian.,Ahmed, Tanveer.,...&Esteban, Miguel A..(2018).NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming.NATURE CELL BIOLOGY,20(4),400-+.

Zhuang, Qiang,et al."NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming".NATURE CELL BIOLOGY 20.4(2018):400-+.