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.

越来越多的癫痫症归因于具有表观遗传功能的基因变异。这些基因的产物包括调节染色质结构和功能以及表观遗传标记的放置、读取和去除以及其他表观遗传过程的因子。在这篇综述中，我们概述了各种表观遗传过程，围绕五个基于功能的类别构建了我们的讨论：DNA 甲基化、组蛋白修饰、组蛋白-DNA 串扰、非编码 RNA 和染色质重塑。我们提供了每个类别的背景信息，描述了每个过程导致基因表达改变的一般机制。我们还强调了关键的临床和机制方面，提供了与每一类癫痫密切相关的基因示例。我们考虑了这些发现的实际应用，包括基于组织和基于生物流体的诊断以及基于精准医学的治疗。我们得出结论，越来越多的人发现表观遗传基因的变异与癫痫有关，对疾病机制、治疗和诊断具有重要意义。