Next generation sequencing in epigenetics: Insights and challenges

The epigenetics community was an early adopter of next generation sequencing (NGS). NGS-based studies have provided detailed and comprehensive views of epigenetic modifications for the genomes of many species and cell types. Recently, DNA methylation has attracted much attention due to the discovery of 5-hydroxymethyl-cytosine and its role in epigenetic reprogramming and pluripotency. This renewed interest has been concomitant with methodological progress enabling, for example, high coverage and single base resolution profiling of the mammalian methylome in small numbers of cells. We summarise this progress and highlight resulting key findings about the complexity of eukaryotic DNA methylation, its role in metazoan genome evolution, epigenetic reprogramming, and its close ties with histone modifications in the context of transcription. Finally, we discuss how fundamental insights gained by NGS, particularly the discovery of widespread allele-specific epigenetic variation in the human genome, have the potential to significantly contribute to the understanding of human common complex diseases.