Coupled single-cell epigenome editing and profiling reveals causal gene regulatory networks [Perturb-ATAC (ATAC)]

Here we present Perturb-ATAC, a method which combines multiplexed CRISPR interference or knockout with genome-wide chromatin accessibility profiling in single cells, based on the simultaneous detection of CRISPR guide RNAs and open chromatin sites by Assay of Transposase-accessible Chromatin with sequencing (ATAC-seq). We applied Perturb-ATAC to transcription factors (TFs), chromatin-modifying factors, and noncoding RNAs (ncRNAs) in ~3,700 single cells, encompassing more than 75 unique genotype-phenotype relationships. Overall design: Single-cell epigenome and perturbation identification in lymphoblastoid cells and epidermal keratinocytes.