期刊
PLOS ONE
卷 13, 期 7, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0201071
关键词
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资金
- Office of the Higher Education Commission [MRG6080118]
- Ratchadaphiseksomphot Endowment Fund Part of the Research Grant for New Scholar CU Researcher's Project [RGN_2557_007_01_37]
- Faculty of Allied Health Sciences Research Fund [AHS-CU 58003]
- 90th Anniversary Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund) [GCUGR1125601058M 53-4, GCUGR1125601055M 53-1, GCUGR1125601056M 53-2]
- Research Assistant Scholarship, Chulalongkorn University
- Graduate School, Chulalongkorn University
- NIEHS [R21 ES023061]
- Thailand Research Fund [MRG6080118, DPG5980005, BRG5980001]
- National Institute of Mental Health [1U24MH081810]
Background The exact cause and mechanisms underlying the pathobiology of autism spectrum disorder (ASD) remain unclear. Dysregulation of long interspersed element-1 (LINE-1) has been reported in the brains of ASD-like mutant mice and ASD brain tissues. However, the role and methylation of LINE-1 in individuals with ASD remain unclear. In this study, we aimed to investigate whether LINE-1 insertion is associated with differentially expressed genes (DEGs) and to assess LINE-1 methylation in ASD. Methods To identify DEGs associated with LINE-1 in ASD, we reanalyzed previously published transcriptome profiles and overlapped them with the list of LINE-1-containing genes from the TranspoGene database. An Ingenuity Pathway Analysis (IPA) of DEGs associated with LINE-1 insertion was conducted. DNA methylation of LINE-1 was assessed via combined bisulfite restriction analysis (COBRA) of lymphoblastoid cell lines from ASD individuals and unaffected individuals, and the methylation levels were correlated with the expression levels of LINE-1 and two LINE-1-inserted DEGs, Clorf27 and ARMC8. Results We found that LINE-1 insertion was significantly associated with DEGs in ASD. The IPA showed that LINE-1-inserted DEGs were associated with ASD-related mechanisms, including sex hormone receptor signaling and axon guidance signaling. Moreover, we observed that the LINE-1 methylation level was significantly reduced in lymphoblastoid cell lines from ASD individuals with severe language impairment and was inversely correlated with the transcript level. The methylation level of LINE-1 was also correlated with the expression of the LINE-1-inserted DEG Clorf27but not ARMC8. Conclusions In ASD individuals with severe language impairment, LINE-1 methylation was reduced and correlated with the expression levels of LINE-1 and the LINE-1-inserted DEG Clorf27. Our findings highlight the association of LINE-1 with DEGs in ASD blood samples and warrant further investigation. The molecular mechanisms of LINE-1 and the effects of its methylation in ASD pathobiology deserve further study.
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