High-throughput Single-cell Chromatin Accessibility CRISPR Screens Enable Unbiased Identification of Regulatory Networks in Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2021 May 21

PMID 34016988

Citations 60

Authors

Sarah E Pierce

Jeffrey M Granja

William J Greenleaf

Affiliations

Soon will be listed here.

Abstract

Chromatin accessibility profiling can identify putative regulatory regions genome wide; however, pooled single-cell methods for assessing the effects of regulatory perturbations on accessibility are limited. Here, we report a modified droplet-based single-cell ATAC-seq protocol for perturbing and evaluating dynamic single-cell epigenetic states. This method (Spear-ATAC) enables simultaneous read-out of chromatin accessibility profiles and integrated sgRNA spacer sequences from thousands of individual cells at once. Spear-ATAC profiling of 104,592 cells representing 414 sgRNA knock-down populations reveals the temporal dynamics of epigenetic responses to regulatory perturbations in cancer cells and the associations between transcription factor binding profiles.

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