High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer.
Sarah E PierceJeffrey M GranjaWilliam J GreenleafPublished in: Nature communications (2021)
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.
Keyphrases
- single cell
- transcription factor
- genome wide
- high throughput
- rna seq
- dna methylation
- induced apoptosis
- dna binding
- gene expression
- cell cycle arrest
- dna damage
- randomized controlled trial
- copy number
- crispr cas
- genome wide identification
- clinical trial
- oxidative stress
- papillary thyroid
- single molecule
- cell death
- cell proliferation
- signaling pathway
- double blind
- pi k akt