Genome‑wide analysis of DNA methylation and gene expression changes in an ovalbumin‑induced asthma mouse model

Kim,Joong‑Sun; Shin,In‑Sik; Shin,Na‑Rae; Nam,Jae‑Yong; Kim,Chul

doi:10.3892/mmr.2020.11245

Genome‑wide analysis of DNA methylation and gene expression changes in an ovalbumin‑induced asthma mouse model

Authors:
- Joong‑Sun Kim
- In‑Sik Shin
- Na‑Rae Shin
- Jae‑Yong Nam
- Chul Kim
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Affiliations: Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju‑si, Jeollanam‑do 58245, Republic of Korea, College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea, Research and Development Center, Insilicogen Inc., Yongin‑si, Gyeonggi‑do 16954, Republic of Korea, Future Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea
Published online on: June 17, 2020 https://doi.org/10.3892/mmr.2020.11245
Pages: 1709-1716
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to establish an integrated network of DNA methylation and RNA expression in an ovalbumin (OVA)‑induced asthma model, and to investigate the epigenetically‑regulated genes involved in asthma development. Genome‑wide CpG‑DNA methylation profiling was conducted through the use of a methylated DNA immunoprecipitation microarray and RNA sequencing was performed using three lung samples from mice with OVA‑induced asthma. A total of 35,401 differentially methylated regions (DMRs) were identified between mice with OVA‑induced asthma and control mice. Of these, 3,060 were located in promoter regions and 370 of the genes containing these DMRs demonstrated an inverse correlation between methylation and gene expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified that 368 genes were upregulated or downregulated in OVA‑induced asthma samples, including genes involved in ‘chemokine signalling pathway’, ‘focal adhesion’, ‘leukocyte transendothelial migration’ and ‘vascular smooth muscle contraction signaling’ pathways. Integrated network analysis identified four hub genes, consisting of three upregulated genes [forkhead box O1 (FOXO1), SP1 transcription factor (SP1) and amyloid β precursor protein (APP)], and one downregulated gene [RUNX family transcription factor 1 (RUNX1)], all of which demonstrated an association between DNA methylation and gene expression. These genes were highly interconnected nodes in the Ingenuity Pathway Analysis module and were functionally significant. A total of four interconnected hub genes, FOXO1, RUNX1, SP1 and APP, were identified from the integrated DNA methylation and gene expression networks involved in asthma development. These results suggested that modulating these four genes could effectively control the development of asthma.

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