MPTP 투여 파킨슨병 마우스 모델에서 유전자 및 DNA methylation 변화 관찰 (Genome-wide analysis of DNA methylation and gene expression changes in MPTP-induced Parkinson’s diseases mouse model)

서지정보

· 발행기관 : 한약정보연구회
· 수록지 정보 : 한약정보연구회지(韓藥情報硏究會誌) / 9권 / 2호 / 209 ~ 220페이지
· 저자명 : 강소희, 김중선, 이지혜, 문창종, 김철

초록

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.

영어초록

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.

참고자료

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