| Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status | |
Qian Y; Zhang J; Hu QL; Xu M; Chen Y; Hu GQ(胡国庆) ; Zhao MR; Liu SJ; Liu, SJ (reprint author), Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China.
| |
| Source Publication | BIOMATERIALS
 |
| 2015-11 | |
| Volume | 70Pages:12-22 |
| ISSN | 0142-9612 |
| Abstract | Silver nanoparticles (nanosilver, AgNPs) have been shown to induce toxicity in vitro and in vivo; however, the molecular bases underlying the detrimental effects have not been thoroughly understood. Although there are numerous studies on its genotoxicity, only a few studies have investigated the epigenetic changes, even less on the changes of histone modifications by AgNPs. In the current study, we probed the AgNP-induced alterations to histone methylation that could be responsible for globin reduction in erythroid cells. AgNP treatment caused a significant reduction of global methylation level for histone 3 (H3) in erythroid MEL cells at sublethal concentrations, devoid of oxidative stress. The ChIP-PCR analyses demonstrated that methylation of H3 at lysine (Lys) 4 (H3K4) and Lys 79 (H3K79) on the beta-globin locus was greatly reduced. The reduction in methylation could be attributed to decreased histone methyltransferase DOT-1L and MLL levels as well as the direct binding between AgNPs to H3/H4 that provide steric hindrance to prevent methylation as predicted by the all-atom molecular dynamics simulations. This direct interaction was further proved by AgNP-mediated pull-down assay and immunoprecipitation assay. These changes, together with decreased RNA polymerase II activity and chromatin binding at this locus, resulted in decreased hemoglobin production. By contrast, Ag ion-treated cells showed no alterations in histone methylation level. Taken together, these results showed a novel finding in which AgNPs could alter the methylation status of histone. Our study therefore opens a new avenue to study the biological effects of AgNPs at sublethal concentrations from the perspective of epigenetic mechanisms. (C) 2015 Elsevier Ltd. All rights reserved. |
| Keyword | Nanosilver Epigenetics Transcription Hemoglobin Histone Methylation |
| DOI | 10.1016/j.biomaterials.2015.08.015 |
| URL | 查看原文 |
| Indexed By | SCI ; EI |
| Language | 英语 |
| WOS ID | WOS:000362610600002 |
| WOS Keyword | BETA-GLOBIN GENE ; MOLECULAR-DYNAMICS ; ENGINEERED NANOMATERIALS ; DOT1L METHYLTRANSFERASE ; CHROMATIN MODIFICATIONS ; EPIGENETIC REGULATION ; GOLD NANOPARTICLES ; H3K79 METHYLATION ; IN-VIVO ; MECHANISMS |
| WOS Research Area | Engineering ; Materials Science |
| WOS Subject | Engineering, Biomedical ; Materials Science, Biomaterials |
| Funding Organization | This work was supported by a grant under the National "973" program (grant number: 2014CB932000), the Strategic Priority Research Program of the Chinese Academy of Sciences (grant number. XDB14000000) and grants from the National Natural Science Foundation of China (grant numbers: 21425731, 21377159, 21321004, 21207152, 21407169). We thank all the laboratory members for their great assistance with experiments and reagents. |
| Department | LNM微纳米流体力学 |
| Classification | 一类 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://dspace.imech.ac.cn/handle/311007/58399 |
| Collection | 非线性力学国家重点实验室 |
| Corresponding Author | Liu, SJ (reprint author), Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China. |
| Recommended Citation GB/T 7714 | Qian Y,Zhang J,Hu QL,et al. Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status[J]. BIOMATERIALS,2015,70:12-22. |
| APA | Qian Y.,Zhang J.,Hu QL.,Xu M.,Chen Y.,...&Liu, SJ .(2015).Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status.BIOMATERIALS,70,12-22. |
| MLA | Qian Y,et al."Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status".BIOMATERIALS 70(2015):12-22. |
| Files in This Item: | Download All | |||||
| File Name/Size | DocType | Version | Access | License | ||
| J2015-042.pdf（2005KB） | 期刊论文 | 作者接受稿 | 开放获取 | CC BY-NC-SA | View Download | |
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment