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

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 [RUN X 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.