Small molecules capable of activating DNA methylation-repressed genes targeted by the p38 mitogen-activated protein kinase pathway
文献类型：期刊论文
| 作者 | Shao, Wei; Wang, Hailin; Zheng, Yong; Li, Xiang; Zhao, Zuodong; Lv, Cong; Lei, Xiaoguang; Zhu, Bing; Zhang, Zhuqiang; Xu, Shaohua |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2018-05-11 |
| 卷号 | 293期号:19页码:7423-7436 |
| 关键词 | DNA methylation high-throughput screening (HTS) p38 mitogen-activated protein kinase (MAPK) gene regulation gene activation |
| ISSN号 | 0021-9258 |
| 文献子类 | Article |
| 英文摘要 | Regulation of gene expression by epigenetic modifications such as DNA methylation is crucial for developmental and disease processes, including cell differentiation and cancer development. Genes repressed by DNA methylation can be derepressed by various compounds that target DNA methyltransferases, histone deacetylases, and other regulatory factors. However, some additional, unknown mechanisms that promote DNA methylation-mediated gene silencing may exist. Chemical agents that can counteract the effects of epigenetic repression that is not regulated by DNA methyltransferases or histone deacetylases therefore may be of research interest. Here, we report the results of a high-throughput screen using a 308,251-member chemical library to identify potent small molecules that derepress an EGFP reporter gene silenced by DNA methylation. Seven hit compounds were identified that did not directly target bulk DNA methylation or histone acetylation. Analyzing the effect of these compounds on endogenous gene expression, we discovered that three of these compounds (compounds LX-3, LX-4, and LX-5) selectively activate the p38 mitogen-activated protein kinase (MAPK) pathway and derepress a subset of endogenous genes repressed by DNA methylation. Selective agonists of the p38 pathway have been lacking, and our study now provides critical compounds for studying this pathway and p38 MAPK-targeted genes repressed by DNA methylation. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/41041]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Shao, Wei,Wang, Hailin,Zheng, Yong,et al. Small molecules capable of activating DNA methylation-repressed genes targeted by the p38 mitogen-activated protein kinase pathway[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(19):7423-7436. |
| APA | Shao, Wei.,Wang, Hailin.,Zheng, Yong.,Li, Xiang.,Zhao, Zuodong.,...&Shang, Erchang.(2018).Small molecules capable of activating DNA methylation-repressed genes targeted by the p38 mitogen-activated protein kinase pathway.JOURNAL OF BIOLOGICAL CHEMISTRY,293(19),7423-7436. |
| MLA | Shao, Wei,et al."Small molecules capable of activating DNA methylation-repressed genes targeted by the p38 mitogen-activated protein kinase pathway".JOURNAL OF BIOLOGICAL CHEMISTRY 293.19(2018):7423-7436. |
入库方式： OAI收割
来源：生态环境研究中心
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