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 ORIGINAL ARTICLE
Year : 2020  |  Volume : 68  |  Issue : 2  |  Page : 307--313

Integrated Genome-Wide DNA Methylation and RNAseq Analysis of Hippocampal Specimens Identifies Potential Candidate Genes and Aberrant Signalling Pathways in Patients with Hippocampal Sclerosis


1 Dr B R Ambedkar Centre for Biomedical Sciences, University of Delhi, Delhi; Center of Excellence for Epilepsy, A Joint NBRC-AIIMS Collaboration, New Delhi, India
2 Center of Excellence for Epilepsy, A Joint NBRC-AIIMS Collaboration; Department of Neurosurgery, AIIMS, New Delhi, India
3 Department of Neurosurgery, AIIMS, New Delhi, India
4 Center of Excellence for Epilepsy, A Joint NBRC-AIIMS Collaboration; Department of Neurology, AIIMS, New Delhi, India
5 Department of Forensic Medicine and Toxicology, AIIMS, New Delhi, India
6 Department of Pathology, AIIMS, New Delhi, India
7 Department of Biophysics, AIIMS, New Delhi, India

Correspondence Address:
Aparna Banerjee Dixit
Dr B R Ambedkar Centre for Biomedical Sciences, University of Delhi, Delhi; Center of Excellence for Epilepsy, A Joint NBRC-AIIMS Collaboration, New Delhi
India
Dr. P Sarat Chandra
Department of Neurosurgery, AIIMS, Room No 605, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.280649

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Background and Aims: DNA methylation and demethylation play a crucial role in the regulation of gene expression, though their interplay during pathogenesis of hippocampal scelerosis (HS) remains elusive. The present study was designed to investigate the DNA methylation regulated changes in expression of HS patients. Methods: We performed integrative analysis of genome-wide CpG-DNA methylation profiling and RNA sequencing to profile global changes in promoter methylation and gene expression in HS patients. Real time PCR was performed to validate the findings of methylation and RNA sequencing. Results: A total of 16040 sites showed altered DNA methylation in all the CpG islands. Of these, 3185 sites were in the promoter regions, of which 66 genes showed an inverse correlation between methylation and expression. These genes are largely related to pathways predicted to participate in axon guidance by semaphorins, MAPK, ionotropic glutamate receptor pathway, notch signaling, regulatory activities related to TFAP2A and immune response, with the most distinct ones included TFAP2A, NRP1, SEMA3B, CACNG2, MAP3K11, and ADAM17. Conclusion: We performed integrated analysis of genomic methylation signature and differential gene expression patterns of hippocampal tissues resected from patients with HS for the first time. Collectively, our findings implicate DNA methylation as a critical regulator of the pathogenic mechanisms of epileptogenesis associated with HS.






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