Single-Cell Epigenomics: Gene Regulation at Unprecedented Resolution

Genome-wide maps of chromatin accessibility represent an unbiased profiling of the “epigenome” and holds tremendous promise for understanding transcriptional regulation. While single-cell gene expression methods have become the major workhorse for understanding complex cell populations in tissues, the underlying regulatory variation that causes this phenotypic heterogeneity remains under explored. In previous work, we developed a robust method for probing the accessible genome of individual cells using a transposase-based method for assaying accessible chromatin (ATAC-seq). Here we discuss recent progress in the development of experimental and computational tools for singe-cell ATAC-seq (scATAC-seq). Furthermore, we discuss applications of these tools to determine important regulatory factors (TFs and cis-regulatory elements) in human samples. Overall, methods for measuring single-cell gene regulation promise to provide the “why” behind the “what” of gene expression, adding unique insight into how cells normally function and how they become altered in disease.