A Study of Alterations in DNA Epigenetic Modifications (5mC and 5hmC) and Gene Expression Influenced by Simulated Microgravity in Human Lymphoblastoid Cells

PLoS One

Arun Seetharam¹  Zhiping Wang²  Joseph Irudayaraj³  Amy C. Lossie³  Basudev Chowdhury⁴  Yunlong Liu⁵  Jyothi Thimmapuram⁵ 

[1] Bindley Biosciences Center, Discovery Park, Purdue University, West Lafayette IN, 47907, United States of America;Bioinformatics Core, Purdue University, West Lafayette, IN, 47907, United States of America;Center for Computational Biology and Bioinformatics, Indiana University School of Medicine Indianapolis, Indianapolis, IN, 46202, United States of America;Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, United States of America;Department of Medical and Molecular Genetics, Indiana University School of Medicine Indianapolis, Indianapolis, IN, 46202, United States of America

关键词: Artificial gravity;    DNA methylation;    Gene expression;    Protein domains;    DNA-binding proteins;    Transcriptional control;    Gene regulation;    DNA transcription;   

DOI  :  10.1371/journal.pone.0147514

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY