NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming
| Autor: | Christina Benda, David P. Ibañez, Zhongzhou Yang, Qiang Zhuang, Micky D. Tortorella, Mazid Md. Abdul, Jiayu Chen, Andrew P. Hutchins, Meng Zhang, Jianguo Zhou, Yan Xu, Xichen Bao, Hui Zhang, Shaorong Gao, Yinghua Huang, Baoming Qin, Zhijian Huang, Jiayin Yang, Xiuling Fu, Ping Liu, Yulin Liu, Xiangpeng Guo, Bushra Mirza, Wenjuan Li, Xiaofen Zhong, Carl Ward, Tanveer Ahmed, Zhiwei Luo, Shahzina Kanwal, Wenxia Fan, Xihua Zhu, Miguel A. Esteban, Muhammad Jadoon Khan, Hung-Fat Tse, Dehao Huang |
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| Rok vydání: | 2018 |
| Předmět: |
Pluripotent Stem Cells
0301 basic medicine Time Factors Somatic cell Kruppel-Like Transcription Factors Histone Deacetylases Epigenesis Genetic Histones Proto-Oncogene Proteins c-myc Kruppel-Like Factor 4 Mice 03 medical and health sciences SOX2 Animals Humans Nuclear Receptor Co-Repressor 1 Nuclear Receptor Co-Repressor 2 Epigenetics Mice Inbred ICR biology SOXB1 Transcription Factors Gene Expression Regulation Developmental Acetylation Mouse Embryonic Stem Cells Cell Biology Cellular Reprogramming HDAC3 Cell biology HEK293 Cells 030104 developmental biology Histone KLF4 biology.protein Octamer Transcription Factor-3 Protein Processing Post-Translational Reprogramming Signal Transduction |
| Zdroj: | Nature Cell Biology. 20:400-412 |
| ISSN: | 1476-4679 1465-7392 |
| Popis: | 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. Zhuang et al. demonstrate that suppression of NCoR/SMRT enhances OSKM reprogramming efficiency, and that the barrier mechanism depends on the recruitment of HDAC3 to pluripotency loci by c-MYC. |
| Databáze: | OpenAIRE |
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