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Title: Defining essential enhancers for pluripotent stem cells using a features-oriented CRISPR-Cas9 screen
Authors: Wang, Hao Fei
Warrier, Tushar
Farran, Chadi A.
Zheng, Zi Hao
Xing, Qiao Rui
Fullwood, Melissa Jane
Zhang, Li-Feng
Li, Hu
Xu, Jian
Lim, Tit-Meng
Loh, Yuin-Han
Keywords: Science::Biological sciences
Issue Date: 2020
Source: Wang, H. F., Warrier, T., Farran, C. A., Zheng, Z. H., Xing, Q. R., Fullwood, M. J., . . . Loh, Y.-H. (2020). Defining essential enhancers for pluripotent stem cells using a features-oriented CRISPR-Cas9 screen. Cell Reports, 33(4), 108309-. doi:10.1016/j.celrep.2020.108309
Project: NRF12018-02
Journal: Cell Reports
Abstract: cis-regulatory elements (CREs) regulate the expression of genes in their genomic neighborhoods and influence cellular processes such as cell-fate maintenance and differentiation. To date, there remain major gaps in the functional characterization of CREs and the identification of their target genes in the cellular native environment. In this study, we perform a features-oriented CRISPR-utilized systematic (FOCUS) screen of OCT4-bound CREs using CRISPR-Cas9 to identify functional enhancers important for pluripotency maintenance in mESCs. From the initial 235 candidates tested, 16 CREs are identified to be essential stem cell enhancers. Using RNA-seq and genomic 4C-seq, we further uncover a complex network of candidate CREs and their downstream target genes, which supports the growth and self-renewal of mESCs. Notably, an essential enhancer, CRE111, and its target, Lrrc31, form the important switch to modulate the LIF-JAK1-STAT3 signaling pathway.
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2020.108309
Schools: School of Biological Sciences 
Organisations: Laboratory for Epigenetics, Stem Cells and Cell Therapy, A*STAR
Rights: © 2020 The Authors. This is an open access article under the CC BY-NC-ND license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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