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

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status
	Qian, Yi; Zhang, Jie; Hu, Qinglin; Xu, Ming; Chen, Yue; Hu, Guoqing; Zhao, Meirong; Liu, Sijin
刊名	BIOMATERIALS
	2015-11
卷号	70 页码:12-22
关键词	Nanosilver Epigenetics Transcription Hemoglobin Histone Methylation
英文摘要	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.
研究领域[WOS]	Engineering, Biomedical ; Materials Science, Biomaterials
WOS记录号	WOS:000362610600002
公开日期	2016-03-15
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/32661]
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	Qian, Yi,Zhang, Jie,Hu, Qinglin,et al. Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status[J]. BIOMATERIALS,2015,70:12-22.
APA	Qian, Yi.,Zhang, Jie.,Hu, Qinglin.,Xu, Ming.,Chen, Yue.,...&Liu, Sijin.(2015).Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status.BIOMATERIALS,70,12-22.
MLA	Qian, Yi,et al."Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status".BIOMATERIALS 70(2015):12-22.