Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status

doi:10.1016/j.biomaterials.2015.08.015

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	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.
发表期刊	BIOMATERIALS
	2015-11
卷号	70 页码:12-22
ISSN	0142-9612
摘要	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.
关键词	Nanosilver Epigenetics Transcription Hemoglobin Histone Methylation
DOI	10.1016/j.biomaterials.2015.08.015
URL	查看原文
收录类别	SCI ; EI
语种	英语
WOS记录号	WOS:000362610600002
关键词[WOS]	BETA-GLOBIN GENE ; MOLECULAR-DYNAMICS ; ENGINEERED NANOMATERIALS ; DOT1L METHYLTRANSFERASE ; CHROMATIN MODIFICATIONS ; EPIGENETIC REGULATION ; GOLD NANOPARTICLES ; H3K79 METHYLATION ; IN-VIVO ; MECHANISMS
WOS研究方向	Engineering ; Materials Science
WOS类目	Engineering, Biomedical ; Materials Science, Biomaterials
项目资助者	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.
课题组名称	LNM微纳米流体力学
论文分区	一类
引用统计	被引频次：73[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://dspace.imech.ac.cn/handle/311007/58399
专题	非线性力学国家重点实验室
通讯作者	Liu, SJ (reprint author), Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China.
推荐引用方式 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.

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