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β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE123692 | GEO | 2020/07/01

REPOSITORIES: GEO

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β-Catenin safeguards the ground state of mousepluripotency by strengthening the robustness of the transcriptional apparatus.

Project description: Not available

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β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus [GRO-seq]

Project description:Mouse embryonic stem cells (ESCs) cultured with MEK and GSK3 inhibitors (2i) more closely resemble the inner cell mass of pre-implantation blastocysts than those cultured with serum/LIF (SL). The transcriptional mechanisms governing this pluripotent ground state are yet unresolved. Release of promoter-proximal paused RNA polymerase II (Pol2) is a multistep process necessary for pluripotency and cell cycle gene transcription in SL. Here, we show that β-catenin, stabilized by GSK3 inhibition in 2i, supplies transcriptional co-regulators including BRD4, CDK9, Mediator, Cohesin, and p300 at pluripotency loci. This selectively strengthens pluripotency loci and renders them addicted to transcription initiation for productive gene body elongation in detriment to Pol2 pause release. By contrast, cell cycle genes are not bound by β-catenin and, thus, proliferation/self-renewal are still tightly controlled by the Pol2 pause release mechanism under 2i conditions. Our findings help to explain how pluripotency is preserved in the ground state and also provide a general model for transcriptional resilience/adaptation upon network perturbation in other biological contexts.

2020-07-01 | GSE140340 | GEO

β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus [ATAC-seq]

Project description: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.

2020-07-01 | GSE123690 | GEO

β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus [RNA-seq]

2020-07-01 | GSE123691 | GEO

β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus

Project description:β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus

| PRJNA509601 | ENA

β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus [GRO-seq]

Project description:β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus [GRO-seq]

| PRJNA589310 | ENA

β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus [ATAC-seq]

Project description:β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus [ATAC-seq]

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β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus [RNA-seq]

Project description:β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus [RNA-seq]

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The transcriptional and epigenomic foundations of ground state pluripotency.

Project description: Not available

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Proteome Analysis of Ground State Pluripotency.

Project description: Not available

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