Stella protein facilitates DNA demethylation by disrupting the chromatin association of the RING finger-type E3 ubiquitin ligase UHRF1
文献类型：期刊论文
| 作者 | Du, Wenlong; Dong, Qiang; Zhang, Zhuqiang; Liu, Baodong; Zhou, Ting; Xu, Rui-ming; Wang, Hailin; Zhu, Bing; Li, Yingfeng |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2019-05-31 |
| 卷号 | 294期号:22页码:8907-8917 |
| ISSN号 | 0021-9258 |
| 关键词 | DNA demethylation DNA methylation gene regulation epigenetics protein-protein interaction chromatin association developmental pluripotency associated 3 (DPPA3) FRAP assay Stella ubiquitin-like with PHD and RING finger domains 1 (UHRF1) |
| 英文摘要 | Stella is a maternal gene required for oogenesis and early embryogenesis. Stella overexpression in somatic cells causes global demethylation. As we have recently shown, Stella sequesters nuclear ubiquitin-like with PHD and RING finger domains 1 (UHRF1), a RING finger-type E3 ubiquitin ligase essential for DNA methylation mediated by DNA methyltransferase 1 and triggers global demethylation. Here, we report an overexpressed mutant Stella protein without nuclear export activity surprisingly retained its ability to cause global demethylation. By combining biochemical interaction assays, isothermal titration calorimetry, immunostaining, and live-cell imaging with fluorescence recovery after photobleaching, we found that Stella disrupts UHRF1's association with chromatin by directly binding to the plant homeodomain of UHRF1 and competing for the interaction between UHRF1 and the histone H3 tail. Consistently, overexpression of Stella mutants that do not directly interact with UHRF1 fails to cause genome-wide demethylation. In the presence of nuclear Stella, UHRF1 could not bind to chromatin and exhibited increased dynamics in the nucleus. Our results indicate that Stella employs a multilayered mechanism to achieve robust UHRF1 inhibition, which involves the dissociation from chromatin and cytoplasmic sequestration of UHRF1. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/43023]  |
| 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 |
| 作者单位 | 1.Chinese Acad Sci, Natl Lab Biomacromol, CAS Ctr Excellence Biomacromol, Inst Biophys, Beijing 100101, Peoples R China 2.Natl Inst Biol Sci, Beijing 102206, Peoples R China 3.Beijing Normal Univ, Coll Life Sci, Beijing 100875, Peoples R China 4.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China 5.Chinese Acad Sci, State Key Lab Environm Chem & Ecotoxicol, Res Ctr Ecoenvironm Sci, Beijing 100085, Peoples R China |
| 推荐引用方式 GB/T 7714 | Du, Wenlong,Dong, Qiang,Zhang, Zhuqiang,et al. Stella protein facilitates DNA demethylation by disrupting the chromatin association of the RING finger-type E3 ubiquitin ligase UHRF1[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2019,294(22):8907-8917. |
| APA | Du, Wenlong.,Dong, Qiang.,Zhang, Zhuqiang.,Liu, Baodong.,Zhou, Ting.,...&Li, Yingfeng.(2019).Stella protein facilitates DNA demethylation by disrupting the chromatin association of the RING finger-type E3 ubiquitin ligase UHRF1.JOURNAL OF BIOLOGICAL CHEMISTRY,294(22),8907-8917. |
| MLA | Du, Wenlong,et al."Stella protein facilitates DNA demethylation by disrupting the chromatin association of the RING finger-type E3 ubiquitin ligase UHRF1".JOURNAL OF BIOLOGICAL CHEMISTRY 294.22(2019):8907-8917. |
入库方式： OAI收割
来源：生态环境研究中心
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