| Literature DB >> 29531310 |
Qiang Zhuang1,2,3,4, Wenjuan Li2,3,5,4, Christina Benda2,3,4, Zhijian Huang2,3,4, Tanveer Ahmed3,4,6,7, Ping Liu2,3,4,8, Xiangpeng Guo1,2,3,4, David P Ibañez2,3,5,4, Zhiwei Luo2,3,5,4, Meng Zhang2,3,5,4, Mazid Md Abdul2,3,5,4, Zhongzhou Yang3, Jiayin Yang9, Yinghua Huang1,3,4,7, Hui Zhang3,4,7, Dehao Huang2,3,5, Jianguo Zhou2,3,4, Xiaofen Zhong2,3, Xihua Zhu2,3,4, Xiuling Fu10, Wenxia Fan2,3,4, Yulin Liu11, Yan Xu2,3,4, Carl Ward2,3,4, Muhammad Jadoon Khan2,3,4, Shahzina Kanwal2,3,4, Bushra Mirza6, Micky D Tortorella12, Hung-Fat Tse9,13,14, Jiayu Chen15, Baoming Qin1,3,4,7,13, Xichen Bao1,2,3,4, Shaorong Gao15, Andrew P Hutchins16, Miguel A Esteban17,18,19,20,21.
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.Entities:
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Year: 2018 PMID： 29531310 DOI： 10.1038/s41556-018-0047-x
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824