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| Status |
Public on Jan 07, 2022 |
| Title |
The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by pausing POL II at pro-differentiation genes [sgRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
In pluripotent cells, a delicate activation-repression balance maintains pro-differentiation genes ready for rapid transcription. The identity of transcription factors (TFs) that specifically repress pro-differentiation genes remains obscure. By targeting ~1,700 TFs with CRISPR loss-of-function perturbations, we found that ZBTB11 and ZFP131 are required to maintain pluripotency in mouse embryonic stem cells (ESCs). ZBTB11 and ZFP131 bind to pro-differentiation genes along with RNA Polymerase II and pausing factor NELF, but without Polycomb repression. Loss of ZBTB11 or ZFP131 leads to a decrease in NELF binding, an increase in H3K4me3, transcriptional upregulation of genes associated with three germ layers, and concomitant ESC differentiation. Together, our results suggest ZBTB11 and ZFP131 maintain pluripotency by pausing pro-differentiation genes transcription and present a generalizable framework to maintain cellular potency.
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| Overall design |
Bulk RNA-seq was used to characterize gene expression in Wildtype, Zbtb10Δ, Zbtb11Δ, and Zfp131Δ cells grown in the presence of +2i+LIF or -2i+LIF.
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| Contributor(s) |
Garipler G, Lu C, Morrisey A, Lopez-Zepeda LS, Vidal SE, Aydin B, Stadtfeld M, Ohler U, Mahony S, Sanjana NE, Mazzoni EO |
| Citation(s) |
35294876 |
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| Submission date |
Nov 06, 2020 |
| Last update date |
Apr 06, 2022 |
| Contact name |
Shaun Mahony |
| E-mail(s) |
mahony@psu.edu
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| Phone |
814-865-3008
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| Organization name |
Penn State University
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| Department |
Biochemistry & Molecular Biology
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| Lab |
Shaun Mahony
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| Street address |
404 South Frear Bldg
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| City |
University Park |
| State/province |
PA |
| ZIP/Postal code |
16802 |
| Country |
USA |
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| Platforms (1) |
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| Samples (5)
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| GSM4886994 |
sgRNAseq of Maxiprep of CRISPR TF library replicate 1 |
| GSM4886995 |
sgRNAseq of Maxiprep of CRISPR TF library replicate 2 |
| GSM4886996 |
sgRNAseq of CRISPR TF transduced ESCs on day 5 post-transduction |
| GSM4886997 |
sgRNAseq of CRISPR TF transduced ESCs on day 8 post-transduction |
| GSM4886998 |
sgRNAseq of CRISPR TF transduced ESCs on day 12 post-transduction |
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| This SubSeries is part of SuperSeries: |
| GSE160966 |
The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by pausing POL II at pro-differentiation genes |
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| Relations |
| BioProject |
PRJNA675005 |
| SRA |
SRP291408 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE160963_RAW.tar |
1.1 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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