Journal
NATURE REVIEWS NEUROLOGY
Volume 18, Issue 9, Pages 530-543Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41582-022-00693-y
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Funding
- Deutsche Forschungsgemeinschaft [FOR 2715]
- Science Foundation Ireland under the European Regional Development Fund [16/RC/3948]
- FutureNeuro industry partners
- European Brain Research Area (EBRA) project
- European Union [825348]
- H2020 Societal Challenges Programme [825348] Funding Source: H2020 Societal Challenges Programme
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An increasing number of epilepsies are being attributed to variants in genes with epigenetic functions. This review provides an overview of various epigenetic processes and how they contribute to altered gene expression in epilepsy. The practical applications of these findings, including diagnostics and treatments, are also discussed.
An increasing number of epilepsies are being attributed to variants in genes with epigenetic functions. The products of these genes include factors that regulate the structure and function of chromatin and the placing, reading and removal of epigenetic marks, as well as other epigenetic processes. In this Review, we provide an overview of the various epigenetic processes, structuring our discussion around five function-based categories: DNA methylation, histone modifications, histone-DNA crosstalk, non-coding RNAs and chromatin remodelling. We provide background information on each category, describing the general mechanism by which each process leads to altered gene expression. We also highlight key clinical and mechanistic aspects, providing examples of genes that strongly associate with epilepsy within each class. We consider the practical applications of these findings, including tissue-based and biofluid-based diagnostics and precision medicine-based treatments. We conclude that variants in epigenetic genes are increasingly found to be causally involved in the epilepsies, with implications for disease mechanisms, treatments and diagnostics. This Review considers how variants in genes encoding proteins that regulate epigenetic mechanisms might contribute to epilepsy. The discussion is structured around five categories of epigenetic mechanisms: DNA methylation, histone modifications, histone-DNA crosstalk, non-coding RNAs and chromatin remodelling.
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