Deep sequencing reveals increased DNA methylation in chronic rat epilepsy

Kobow, Katja, Kaspi, Antony, Harikrishnan, K. N., Kiese, Katharina, Ziemann, Mark, Khurana, Ishant, Fritzsche, Ina, Hauke, Jan, Hahnen, Eric, Coras, Roland, Mühlebner, Angelika, El-Osta, Assam and Blümcke, Ingmar 2013, Deep sequencing reveals increased DNA methylation in chronic rat epilepsy, Acta neuropathologica, vol. 126, no. 5, pp. 741-756, doi: 10.1007/s00401-013-1168-8.

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Title Deep sequencing reveals increased DNA methylation in chronic rat epilepsy
Author(s) Kobow, Katja
Kaspi, Antony
Harikrishnan, K. N.
Kiese, Katharina
Ziemann, MarkORCID iD for Ziemann, Mark
Khurana, Ishant
Fritzsche, Ina
Hauke, Jan
Hahnen, Eric
Coras, Roland
Mühlebner, Angelika
El-Osta, Assam
Blümcke, Ingmar
Journal name Acta neuropathologica
Volume number 126
Issue number 5
Start page 741
End page 756
Total pages 16
Publisher Springer
Place of publication New York, N. Y.
Publication date 2013-11
ISSN 1432-0533
Keyword(s) Animals
DNA Methylation
Diet, Ketogenic
Disease Models, Animal
Epigenesis, Genetic
High-Throughput Nucleotide Sequencing
Rats, Wistar
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences & Neurology
Massive parallel sequencing
Summary 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.
Language eng
DOI 10.1007/s00401-013-1168-8
Field of Research 1103 Clinical Sciences
1109 Neurosciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2013, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
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