Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver.

IF 4.8 Q1 GENETICS & HEREDITY Environmental Epigenetics Pub Date : 2021-09-17 eCollection Date: 2021-01-01 DOI:10.1093/eep/dvab008
Carolyn M Klinge, Kellianne M Piell, Belinda J Petri, Liqing He, Xiang Zhang, Jianmin Pan, Shesh N Rai, Kalina Andreeva, Eric C Rouchka, Banrida Wahlang, Juliane I Beier, Matthew C Cave
{"title":"Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver.","authors":"Carolyn M Klinge, Kellianne M Piell, Belinda J Petri, Liqing He, Xiang Zhang, Jianmin Pan, Shesh N Rai, Kalina Andreeva, Eric C Rouchka, Banrida Wahlang, Juliane I Beier, Matthew C Cave","doi":"10.1093/eep/dvab008","DOIUrl":null,"url":null,"abstract":"<p><p>Exposure to a single dose of polychlorinated biphenyls (PCBs) and a 12-week high-fat diet (HFD) results in nonalcoholic steatohepatitis (NASH) in mice by altering intracellular signaling and inhibiting epidermal growth factor receptor signaling. Post-transcriptional chemical modification (PTM) of RNA regulates biological processes, but the contribution of epitranscriptomics to PCB-induced steatosis remains unknown. This study tested the hypothesis that PCB and HFD exposure alters the global RNA epitranscriptome in male mouse liver. C57BL/6J male mice were fed a HFD for 12 weeks and exposed to a single dose of Aroclor 1260 (20 mg/kg), PCB 126 (20 µg/kg), both Aroclor 1260 and PCB 126 or vehicle control after 2 weeks on HFD. Chemical RNA modifications were identified at the nucleoside level by liquid chromatography-mass spectrometry. From 22 PTM global RNA modifications, we identified 10 significant changes in RNA modifications in liver with HFD and PCB 126 exposure. Only two modifications were significantly different from HFD control liver in all three PCB exposure groups: 2'-O-methyladenosine (Am) and N(6)-methyladenosine (m6A). Exposure to HFD + PCB 126 + Aroclor 1260 increased the abundance of N(6), O(2)-dimethyladenosine (m6Am), which is associated with the largest number of transcript changes. Increased m6Am and pseudouridine were associated with increased protein expression of the writers of these modifications: Phosphorylated CTD Interacting Factor 1 (PCIF1) and Pseudouridine Synthase 10 (PUS10), respectively, in HFD + PCB 126- + Aroclor 1260-exposed mouse liver. Increased N1-methyladenosine (m1A) and m6A were associated with increased transcript levels of the readers of these modifications: YTH N6-Methyladenosine RNA Binding Protein 2 (YTHDF2), YTH Domain Containing 2 (YTHDC2), and reader FMRP Translational Regulator 1 (FMR1) transcript and protein abundance. The results demonstrate that PCB exposure alters the global epitranscriptome in a mouse model of NASH; however, the mechanism for these changes requires further investigation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448424/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environmental Epigenetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/eep/dvab008","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

Exposure to a single dose of polychlorinated biphenyls (PCBs) and a 12-week high-fat diet (HFD) results in nonalcoholic steatohepatitis (NASH) in mice by altering intracellular signaling and inhibiting epidermal growth factor receptor signaling. Post-transcriptional chemical modification (PTM) of RNA regulates biological processes, but the contribution of epitranscriptomics to PCB-induced steatosis remains unknown. This study tested the hypothesis that PCB and HFD exposure alters the global RNA epitranscriptome in male mouse liver. C57BL/6J male mice were fed a HFD for 12 weeks and exposed to a single dose of Aroclor 1260 (20 mg/kg), PCB 126 (20 µg/kg), both Aroclor 1260 and PCB 126 or vehicle control after 2 weeks on HFD. Chemical RNA modifications were identified at the nucleoside level by liquid chromatography-mass spectrometry. From 22 PTM global RNA modifications, we identified 10 significant changes in RNA modifications in liver with HFD and PCB 126 exposure. Only two modifications were significantly different from HFD control liver in all three PCB exposure groups: 2'-O-methyladenosine (Am) and N(6)-methyladenosine (m6A). Exposure to HFD + PCB 126 + Aroclor 1260 increased the abundance of N(6), O(2)-dimethyladenosine (m6Am), which is associated with the largest number of transcript changes. Increased m6Am and pseudouridine were associated with increased protein expression of the writers of these modifications: Phosphorylated CTD Interacting Factor 1 (PCIF1) and Pseudouridine Synthase 10 (PUS10), respectively, in HFD + PCB 126- + Aroclor 1260-exposed mouse liver. Increased N1-methyladenosine (m1A) and m6A were associated with increased transcript levels of the readers of these modifications: YTH N6-Methyladenosine RNA Binding Protein 2 (YTHDF2), YTH Domain Containing 2 (YTHDC2), and reader FMRP Translational Regulator 1 (FMR1) transcript and protein abundance. The results demonstrate that PCB exposure alters the global epitranscriptome in a mouse model of NASH; however, the mechanism for these changes requires further investigation.

Abstract Image

Abstract Image

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
多氯联苯和高脂肪饮食的联合暴露改变了小鼠肝脏的整体表转录组学景观。
暴露于单剂量多氯联苯(PCBs)和12周高脂肪饮食(HFD)会通过改变细胞内信号传导和抑制表皮生长因子受体信号传导导致小鼠非酒精性脂肪性肝炎(NASH)。RNA的转录后化学修饰(PTM)调节生物过程,但表观转录组学对多氯联苯诱导的脂肪变性的贡献尚不清楚。本研究验证了PCB和HFD暴露改变雄性小鼠肝脏整体RNA表转录组的假设。C57BL/6J雄性小鼠连续喂食HFD 12周,在连续喂食HFD 2周后,分别给予单剂量Aroclor 1260 (20 mg/kg)、PCB 126(20µg/kg)、Aroclor 1260和PCB 126或对照。采用液相色谱-质谱联用技术在核苷水平鉴定了化学RNA修饰。从22个PTM全局RNA修饰中,我们确定了HFD和PCB 126暴露后肝脏中RNA修饰的10个显著变化。在所有三个PCB暴露组中,只有两种修饰与HFD对照肝有显著差异:2'- o -甲基腺苷(Am)和N(6)-甲基腺苷(m6A)。暴露于HFD + PCB 126 + Aroclor 1260增加了N(6), O(2)-二甲基腺苷(m6Am)的丰度,这与转录物变化的数量最多有关。在HFD + PCB 126- + Aroclor 1260暴露的小鼠肝脏中,m6Am和伪尿嘧啶的增加分别与磷酸化CTD相互作用因子1 (PCIF1)和伪尿嘧啶合成酶10 (PUS10)的蛋白表达增加有关。增加的n1 -甲基腺苷(m1A)和m6A与这些修饰的读取器的转录水平增加有关:YTH n6 -甲基腺苷RNA结合蛋白2 (YTHDF2), YTH结构域2 (YTHDC2),以及读取器FMRP翻译调节因子1 (FMR1)转录物和蛋白质丰度。结果表明,PCB暴露改变了NASH小鼠模型的全局表转录组;然而,这些变化的机制需要进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Environmental Epigenetics
Environmental Epigenetics GENETICS & HEREDITY-
CiteScore
6.50
自引率
5.30%
发文量
0
审稿时长
17 weeks
期刊最新文献
Correction to: To live or let die? Epigenetic adaptations to climate change-a review. Bronchial cell epigenetic aging in a human experimental study of short-term diesel and ozone exposures. Epigenetic transgenerational inheritance of toxicant exposure-specific non-coding RNA in sperm. Environmental conditions elicit a slow but enduring response of histone post-translational modifications in Mozambique tilapia. Impaired energy expenditure following exposure to either DDT or DDE in mice may be mediated by DNA methylation changes in brown adipose.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1