Deep sequencing reveals increased DNA methylation in chronic rat epilepsy
journal contributionposted on 2013-11-01, 00:00 authored by Katja Kobow, Antony Kaspi, K N Harikrishnan, Katharina Kiese, Mark ZiemannMark Ziemann, Ishant Khurana, Ina Fritzsche, Jan Hauke, Eric Hahnen, Roland Coras, Angelika Mühlebner, Assam El-Osta, Ingmar Blümcke
Epilepsy is a frequent neurological disorder, although onset and progression of seizures remain difficult to predict in affected patients, irrespective of their epileptogenic condition. Previous studies in animal models as well as human epileptic brain tissue revealed a remarkably diverse pattern of gene expression implicating epigenetic changes to contribute to disease progression. Here we mapped for the first time global DNA methylation patterns in chronic epileptic rats and controls. Using methyl-CpG capture associated with massive parallel sequencing (Methyl-Seq) we report the genomic methylation signature of the chronic epileptic state. We observed a predominant increase, rather than loss of DNA methylation in chronic rat epilepsy. Aberrant methylation patterns were inversely correlated with gene expression changes using mRNA sequencing from same animals and tissue specimens. Administration of a ketogenic, high-fat, low-carbohydrate diet attenuated seizure progression and ameliorated DNA methylation mediated changes in gene expression. This is the first report of unsupervised clustering of an epigenetic mark being used in epilepsy research to separate epileptic from non-epileptic animals as well as from animals receiving anti-convulsive dietary treatment. We further discuss the potential impact of epigenetic changes as a pathogenic mechanism of epileptogenesis.
Pagination741 - 756
LocationNew York, N. Y.
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Publication classificationC1.1 Refereed article in a scholarly journal
Copyright notice2013, The Authors
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AnimalsDNA MethylationDiet, KetogenicDisease Models, AnimalEpigenesis, GeneticEpilepsyHigh-Throughput Nucleotide SequencingMaleRatsRats, WistarTranscriptomeScience & TechnologyLife Sciences & BiomedicineClinical NeurologyNeurosciencesPathologyNeurosciences & NeurologyHippocampusEpigeneticMassive parallel sequencingKetogenic dietTEMPORAL-LOBE EPILEPSYDIFFERENTIAL EXPRESSION ANALYSISGENE-EXPRESSIONHISTONE MODIFICATIONSCHROMATINPROMOTERSEIZURESEPILEPTOGENESISINTERLEUKIN-10