BROWSE

Related Researcher

Author's Photo

Cho, Seung Woo
Research Interests

ITEM VIEW & DOWNLOAD

Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks

Cited 0 times inthomson ciCited 0 times inthomson ci
Title
Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks
Author
Rubin, Adam J.Parker, Kevin R.Satpathy, Ansuman T.Qi, YanyanWu, BeijingOng, Alvin J.Mumbach, Maxwell R.Ji, Andrew L.Kim, Daniel S.Cho, Seung WooZarnegar, Brian J.Greenleaf, William J.Chang, Howard Y.Khavari, Paul A.
Keywords
single-cell genomics;  CRISPR;  pooled screens;  epigenomics;  ATAC-seq;  chromatin accessibility
Issue Date
201901
Publisher
CELL PRESS
Citation
CELL, v.176, no.1-2, pp.361 - 376
Abstract
Here, we present Perturb-ATAC, a method that 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 ∼4,300 single cells, encompassing more than 63 genotype-phenotype relationships. Perturb-ATAC in human B lymphocytes uncovered regulators of chromatin accessibility, TF occupancy, and nucleosome positioning and identified a hierarchy of TFs that govern B cell state, variation, and disease-associated cis-regulatory elements. Perturb-ATAC in primary human epidermal cells revealed three sequential modules of cis-elements that specify keratinocyte fate. Combinatorial deletion of all pairs of these TFs uncovered their epistatic relationships and highlighted genomic co-localization as a basis for synergistic interactions. Thus, Perturb-ATAC is a powerful strategy to dissect gene regulatory networks in development and disease.
URI
Go to Link
DOI
http://dx.doi.org/10.1016/j.cell.2018.11.022
ISSN
0092-8674
Appears in Collections:
SLS_Journal Papers
Files in This Item:
There are no files associated with this item.

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qr_code

  • mendeley

    citeulike

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

MENU