Editing the Epigenome: Overview, Open Questions, and Directions of Future Development.

The introduction of CRISPR/Cas has resulted in a strong impulse for the field of gene-targeted epigenome reprogramming. In this approach EpiEditors are applied in cells, which consist of a DNA-binding part for targeting and a functional part to induce chromatin modifications at targeted genome loci. The accumulating evidence of epigenetic reprogramming of a given genomic locus resulting in gene expression changes indicated causal relationships of epigenetic marks instructing gene expression and opened the field for mainstream applications. In this perspective, an overview of the current status of the field is provided, including its applications and future perspectives. The dependence of critical parameters like specificity, effectivity, and sustainability of epigenome editing on experimental settings and conditions including the expression levels and the duration of the expression of the EpiEditors, their DNA-binding affinity and specificity, and the cross talk between EpiEditors and cellular chromatin modifiers is discussed. Once established in fully functional "plug-and-play" mode, epigenome editing will allow to better understand epigenetic expression control and to translate such knowledge into therapeutic tools.