Inhibition of Ezh2 In Vitro and the Decline of Ezh2 in Developing Midbrain Promote Dopaminergic Neurons Differentiation Through Modifying H3K27me3
文献类型：期刊论文
| 作者 | Hong, Feng1,2; Zhao, Mengxue1,2; Zhang, Lei1; Feng, Linyin1,2
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| 刊名 | STEM CELLS AND DEVELOPMENT
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| 出版日期 | 2019-05-15 |
| 卷号 | 28期号:10页码:649-658 |
| 关键词 | dopaminergic neurons Ezh2 Nurr1 neural stem cells |
| ISSN号 | 1547-3287 |
| DOI | 10.1089/scd.2018.0258 |
| 通讯作者 | Feng, Linyin(lyfeng@simm.ac.cn) |
| 英文摘要 | Epigenetic modifications play an important role in neural development. Trimethylated histone H3 at lysine 27 (H3K27me3) is a repressive epigenetic marker that mediates tissue development. In this study, we demonstrate that H3K27me3 and histone methyl transferase Ezh2 regulated the development of dopaminergic (DA) neurons in vitro and in vivo. We found that H3K27me3 increased during differentiation of ventral midbrain-derived neural stem cells (VM-NSCs). However, histone demethylase selective inhibitor GSK-J1 increased H3K27me3 level and decreased the expression of tyrosine hydroxylase. Treated with Ezh2-selective inhibitor EPZ005687 repressed the trimethylation of H3K27 and enhanced differentiation of DA neurons in VM-NSCs cultures. Furthermore, Ezh2 inhibition promoted the expression of DA neurons developmental-related factors by modifying H3K27 trimethylation on the relevant promoter regions. Moreover, the effect of Ezh2 inhibition-mediated DA neurons differentiation was blocked by the expression of shRNA specific for Nurr1. In vivo, Ezh2 decreased and resulted in a reduction of H3K27me3 in developing midbrain. Deletion of Ezh2 by RNA interference approach promoted differentiation of DA neurons during midbrain development. Overexpression of Ezh2 enhanced cell self-renewal and did not affect differentiation of DA neurons. |
| WOS关键词 | STEM-CELLS ; HISTONE METHYLTRANSFERASE ; HIPPOCAMPAL NEUROGENESIS ; SELF-RENEWAL ; GENE ; METHYLATION ; JMJD3 ; PROLIFERATION ; DEMETHYLASES ; MAINTENANCE |
| 资助项目 | Key New Drug Creation and Manufacturing Program of the National Science and Technology Major Project[2014ZX09102-001-05] ; Scientific Innovation Project of the Chinese Academy of Sciences[XDA01040304] |
| WOS研究方向 | Cell Biology ; Hematology ; Research & Experimental Medicine ; Transplantation |
| 语种 | 英语 |
| WOS记录号 | WOS:000465532300001 |
| 出版者 | MARY ANN LIEBERT, INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/288512]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Feng, Linyin |
| 作者单位 | 1.Univ Chinese Acad Sci, Shanghai Inst Materia Med, Dept Neuropharmacol, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Shanghai Inst Materia Med, Dept Neuropharmacol, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hong, Feng,Zhao, Mengxue,Zhang, Lei,et al. Inhibition of Ezh2 In Vitro and the Decline of Ezh2 in Developing Midbrain Promote Dopaminergic Neurons Differentiation Through Modifying H3K27me3[J]. STEM CELLS AND DEVELOPMENT,2019,28(10):649-658. |
| APA | Hong, Feng,Zhao, Mengxue,Zhang, Lei,&Feng, Linyin.(2019).Inhibition of Ezh2 In Vitro and the Decline of Ezh2 in Developing Midbrain Promote Dopaminergic Neurons Differentiation Through Modifying H3K27me3.STEM CELLS AND DEVELOPMENT,28(10),649-658. |
| MLA | Hong, Feng,et al."Inhibition of Ezh2 In Vitro and the Decline of Ezh2 in Developing Midbrain Promote Dopaminergic Neurons Differentiation Through Modifying H3K27me3".STEM CELLS AND DEVELOPMENT 28.10(2019):649-658. |
入库方式： OAI收割
来源：上海药物研究所
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