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| Status |
Public on Jul 01, 2020 |
| Title |
β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Mouse embryonic stem cells (ESCs) cultured with inhibitors of MEK and GSK3 (2iL) more closely resemble the pre-implantation embryo inner cell mass than cultures in serum/LIF (SL). Unveiling the differences between both systems is important for understanding development and could also assist in isolating an ESC equivalent for other mammalian species. In SL, pluripotency and cell cycle gene transcription is a multistep process requiring release of promoter-proximal paused RNA polymerase II (Pol2) by the histone acetylation reader BRD4 and the Pol2 kinase CDK9. Here, we show that recruitment of co-regulators including Mediator and Cohesin by β-catenin changes the mode of transcriptional regulation at BRD4/CDK9-bound loci in 2iL. This switch renders pluripotency genes more reliant on transcriptional initiation and less on Pol2 pause release for effective gene body elongation. Conversely, cell cycle genes are not bound by β-catenin and are still dependent on Pol2 pause release. Thus, pluripotency is more resistant to BRD4/CDK9 suppression in 2iL while self-renewal remains highly sensitive. Our findings help to explain how pluripotency is shielded in the ground state and provide insight into transcriptional adaptation upon network perturbation in other contexts.
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| Overall design |
RNA-seq of mouse embryonic stem cells (ESCs) cultured either with inhibitors of MEK and GSK3 (2iL) or cultured in serum/LIF (SL), and treated with DMSO or JQ1 (100nM).
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| Contributor(s) |
Lai Y |
| Citation(s) |
32832621 |
| Submission date |
Dec 12, 2018 |
| Last update date |
Sep 08, 2020 |
| Contact name |
Yiwei Lai |
| E-mail(s) |
lai_yiwei@gibh.ac.cn
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| Organization name |
Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences
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| Department |
South China Institute for Stem Cell Biology and Regenerative Medicine Key Laboratory of Regenerative Biology, CAS
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| Lab |
Miguel
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| Street address |
190 Kai Yuan Avenue, Science Park
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510530 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE123692 |
β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus |
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| Relations |
| BioProject |
PRJNA509604 |
| SRA |
SRP173317 |
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