Epigenetic alterations associated with dexamethasone sodium phosphate through DNMT and TET in RPE cells.

IF 1.8 3区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Vision Pub Date : 2021-11-20 eCollection Date: 2021-01-01
Wenjie Liu, Sruthi Priya Mohan, Nareshkumar Ragavachetty Nagaraj, Shyam Sundar Jaganathan, Yi Wen, Sharada Ramasubramanyan, Joseph Irudayaraj
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Abstract

Purpose: To elucidate the mechanism behind epigenetic alteration associated with dexamethasone (DEX) sodium phosphate treatment.

Methods: We performed enzyme-linked immunosorbent assay to quantify changes in global DNA methylation and hydroxymethylation, quantitative real-time PCR (qRT-PCR) of the DNA methylation- and hydroxymethylation-related gene, in vitro DNA methyltransferase (DNMT) enzymatic activity assays with purified DNMTs, and DNA hydroxymethylation pattern with super-resolution imaging.

Results: We identified global DNA hypomethylation and hyper-hydroxymethylation upon DEX treatment, associated with aberrant mRNA expression levels of DNMT and ten-eleven translocation (TET) proteins. Additionally, DEX exposure could directly hinder DNMT activities.

Conclusions: We showed that DEX-induced epigenetic alterations are linked to aberrant DNMT and TET expression, potentially through an essential role of DNMT.

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RPE细胞中通过DNMT和TET与地塞米松磷酸钠相关的表观遗传改变。
目的:阐明与地塞米松磷酸钠治疗相关的表观遗传改变的机制。方法:采用酶联免疫吸附法定量测定DNA甲基化和羟甲基化的变化,采用实时荧光定量PCR (qRT-PCR)检测DNA甲基化和羟甲基化相关基因,用纯化的DNA甲基转移酶(DNMT)进行体外DNA甲基转移酶(DNMT)酶活性测定,并采用超分辨率成像技术检测DNA羟甲基化模式。结果:我们发现,DEX治疗后,DNA整体低甲基化和超羟甲基化与DNMT和TET蛋白mRNA表达水平异常相关。此外,DEX暴露可直接阻碍DNMT的活性。结论:我们发现dex诱导的表观遗传改变与DNMT和TET的异常表达有关,可能通过DNMT的重要作用。
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来源期刊
Molecular Vision
Molecular Vision 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
25
审稿时长
1 months
期刊介绍: Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical). Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints. For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.
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