Characterizing cis-regulatory elements using single-cell epigenomics

Cell type-specific gene expression patterns and dynamics during development or in disease are controlled by cis -regulatory elements (CREs), such as promoters and enhancers. Distinct classes of CREs can be characterized by their epigenomic features, including DNA methylation, chromatin accessibility, combinations of histone modifications and conformation of local chromatin. Tremendous progress has been made in cataloguing CREs in the human genome using bulk transcriptomic and epigenomic methods. However, single-cell epigenomic and multi-omic technologies have the potential to provide deeper insight into cell type-specific gene regulatory programmes as well as into how they change during development, in response to environmental cues and through disease pathogenesis. Here, we highlight recent advances in single-cell epigenomic methods and analytical tools and discuss their readiness for human tissue profiling. In this Review, Preissl, Gaulton and Ren discuss single-cell epigenomic methods and data analysis tools, their readiness for profiling cis -regulatory elements in human tissues and the insight they can provide into dynamic, context-specific gene regulation.