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KMID : 1145720210090020209
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Korean Herbal Medicine Informatics
2021 Volume.9 No. 2 p.209 ~ p.220
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Genome-wide analysis of DNA methylation and gene expression changes in MPTP-induced Parkinson’s diseases mouse model
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Kang So-Hi
Kim Joong-Sun
Lee Ji-Hye
Moon Chang-Jong
Kim Chul
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Abstract
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This study aimed to establish an integrated network of DNA methylation and RNA expression in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) model and investigate epigenetically-regulated genes involved in PD development. In this model, MPTP impaired motor coordination as demonstrated by the rota-rod behavioral test. MPTP also decreased the expression of tyrosine hydroxylase (TH) positive neurons in the substantia nigra (SN) of mice. We conducted genome-wide CpG-DNA methylation profiling through methylated DNA immunoprecipitation microarray and RNA sequencing using two substantia nigra samples from mice with MPTP-induced Parkinson’s disease. We profiled genome-wide DNA methylation using Methyl-Seq and measured the transcriptome using RNA-Seq in murine SN in the following groups: vehicle-treated mice and MPTP-induced PD mice. In total, 280 differentially expressed genes were identified in association with the PD effect of MPTP. Among them, 201 were positively correlated, and 79 were negatively correlated downregulated genes. A total of 1,773 differentially methylated regions (DMRs) were identified between mice with control and MPTP-induced PD mice. Of these, 474 were hypermethylated, and 398 were hypomethylated DMR. A total of three interconnected genes, autophagy related 7 (atg7), tumor necrosis factor ligand superfamily member 12 (tnfsf12), and diglyceride kinase eta (dgkh), were identified from the integrated DNA methylation and gene expression networks involved Parkinson’s disease development. These results indicate that modulating just three genes can effectively control the development of Parkinson’s disease.
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KEYWORD
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Parkinson’s disease, Animal disease model, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, DNA methylation
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