Abstract
Hippocampal sclerosis (HS) is one of the most prevalent pathological types of temporal lobe epilepsy (TLE), and it significantly affects patient prognoses. The methylation of DNA plays an important role in the development of epilepsy. However, few studies have focused on HS subtypes to determine DNA methylation profiles in TLE. This study aimed to determine the pathogenesis of TLE from an epigenetic perspective in patients with TLE-HS type I (TLE-HSTI) and TLE without HS (TLE-nHS) using whole-genome bisulfite sequencing (WGBS). We defined 1171 hypermethylated and 2537 hypomethylated regions and found 632 differentially methylated genes (DMG) in the promoter region that were primarily involved in the regulation of various aspects of epilepsy development. Twelve DMG overlapped with differentially expressed genes (DEG) in the promoter region, and RT-qPCR findings revealed significant overexpression of the SBNO2, CBX3, RASAL3, and TMBIM4 genes in TLE-HSTI. We present the first systematic analysis of methylation profiles of TLE-HSTI and TLE-nHS from an epigenetic perspective using WGBS. Overall, our preliminary data highlight the underlying mechanism of TLE-HSTI, providing a new perspective for guiding treatment of TLE.
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The raw data are publicly available in the GEO, under accession number GSE140658.
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Acknowledgments
We are grateful to all the patients for their participation in the investigation, and the staff for excellent technical assistance and sample collection.
Funding
This work was supported by the National Nature Science Foundation of China (no. 81601130, U20A20383 and 81571646), Natural Science Foundation of Heilongjiang Province (no. LH2019H082), Certificate of China Postdoctoral Science Foundation Grant (no. 2018M631951), Financial Assistance under Heilongjiang Postdoctoral Fund (no. LBH-Z17144), and Innovation Fund of the First Affiliated Hospital of Harbin Medical University (no. 2020L06).
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Meng Na, Zhiguo Lin, and Hong Shen conceived and designed the study; Chongyang Tang and Zhenfeng Jiang analyzed the data; Miaomiao Jiang, Shi Yan, and Haiyang Wang carried out immunohistochemical experiments; Wang Zhang created the figures and wrote the manuscript; Alicia Y. Hou revised the language of the manuscript; Binchao Liu, Xian Han, and Yifei Gu conducted the assays and contributed to data acquisition. All authors read and approved the final manuscript.
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All subjects in this study provided their written informed consent. The study protocol was approved by the Ethics Committee of the First Clinical College of Harbin Medical University.
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Supplementary file1 Supplementary Figure 1 Classification of methylated cytosines. Three samples each from patients with TLE-HSTI (A, B, and C), and TLE-nHS (D, E, and F). Colors represent methylated C sites under different contexts, and the area of each part represents the proportion of methylated C sites under the corresponding context. C, cytosine (TIF 490 KB)
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Supplementary file2 Supplementary Figure 2 Heat map of DNA methylation profiles in sequence context. CGI, CpG island (TIF 1373 KB)
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Supplementary file3 Supplementary Figure 3 Distribution of DMR among genomic regions. CGI, CpG island; DMR, differentially expressed regions (TIF 1151 KB)
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Supplementary file4 Supplementary Figure 4 Gene Ontology classification and KEGG pathway enrichment of DMG based on CG (A, B) and in promoter region (C, D). CG, cytosine-guanine DMG, differentially methylated genes; KEGG, Kyoto Encyclopedia of Genes and Genomes (TIF 1229 KB)
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Zhang, W., Wang, H., Liu, B. et al. Differential DNA Methylation Profiles in Patients with Temporal Lobe Epilepsy and Hippocampal Sclerosis ILAE Type I. J Mol Neurosci 71, 1951–1966 (2021). https://doi.org/10.1007/s12031-020-01780-9
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DOI: https://doi.org/10.1007/s12031-020-01780-9