A Study of Alterations in DNA Epigenetic Modifications (5mC and 5hmC) and Gene Expression Influenced by Simulated Microgravity in Human Lymphoblastoid Cells.
A Study of Alterations in DNA Epigenetic Modifications (5mC and 5hmC) and Gene Expression Influenced by Simulated Microgravity in Human Lymphoblastoid Cells.
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DOI：
10.1371/journal.pone.0147514
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Irudayaraj J
中科院分区：
文献类型：
--
作者：
Chowdhury B;Seetharam A;Wang Z;Liu Y;Lossie AC;Thimmapuram J;Irudayaraj J
细胞改变其基因表达以响应暴露于各种环境变化。表观遗传机制如DNA甲基化被认为调节基因表达模式的改变。体外和体内研究记录了在空间经历的微重力条件影响下细胞增殖、细胞骨架重塑、信号转导、骨矿化和免疫缺陷等方面的变化。然而，微重力引起的表观基因组变化尚未得到很好的表征。在这项研究中，我们已经使用下一代测序（NGS）的轮廓地面“模拟”微重力引起的DNA甲基化（5-甲基胞嘧啶或5 mC），羟甲基化（5-羟甲基胞嘧啶或5 hmC）的变化，并在培养的人类淋巴母细胞的同时基因表达。我们的研究结果表明，模拟微重力诱导甲基化组的改变（约60%的差异甲基化区域或DMR是低甲基化的，约92%的差异羟甲基化区域或DHMR是超羟甲基化的）。模拟微重力还诱导了370种转录物的差异表达，这些转录物与氧化应激反应、碳水化合物代谢和转录调节等关键生物过程有关。虽然我们无法获得任何与甲基化/羟基化变化与基因表达相关的全球趋势，但我们已经能够对一些差异表达基因进行模拟微重力诱导的5 mC变化进行分析，这些差异表达基因包括在其启动子上经历差异甲基化的5个基因和在其基因体上经历差异甲基化的25个基因。据我们所知，这是第一个基于NGS的研究，以描述短时间暴露于模拟微重力下诱导的表观基因组模式，我们相信我们的研究结果可以成为未来探索的宝贵资源。
Cells alter their gene expression in response to exposure to various environmental changes. Epigenetic mechanisms such as DNA methylation are believed to regulate the alterations in gene expression patterns. In vitro and in vivo studies have documented changes in cellular proliferation, cytoskeletal remodeling, signal transduction, bone mineralization and immune deficiency under the influence of microgravity conditions experienced in space. However microgravity induced changes in the epigenome have not been well characterized. In this study we have used Next-generation Sequencing (NGS) to profile ground-based “simulated” microgravity induced changes on DNA methylation (5-methylcytosine or 5mC), hydroxymethylation (5-hydroxymethylcytosine or 5hmC), and simultaneous gene expression in cultured human lymphoblastoid cells. Our results indicate that simulated microgravity induced alterations in the methylome (~60% of the differentially methylated regions or DMRs are hypomethylated and ~92% of the differentially hydroxymethylated regions or DHMRs are hyperhydroxymethylated). Simulated microgravity also induced differential expression in 370 transcripts that were associated with crucial biological processes such as oxidative stress response, carbohydrate metabolism and regulation of transcription. While we were not able to obtain any global trend correlating the changes of methylation/ hydroxylation with gene expression, we have been able to profile the simulated microgravity induced changes of 5mC over some of the differentially expressed genes that includes five genes undergoing differential methylation over their promoters and twenty five genes undergoing differential methylation over their gene-bodies. To the best of our knowledge, this is the first NGS-based study to profile epigenomic patterns induced by short time exposure of simulated microgravity and we believe that our findings can be a valuable resource for future explorations.