β-Catenin safeguards the ground state of mousepluripotency by strengthening the robustness of the transcriptional apparatus
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- dc.contributor.author Zhang, Meng
- dc.contributor.author Arumugam, Karthik
- dc.contributor.author Di Vicino, Umberto
- dc.contributor.author Cosma, Maria Pia, 1970-
- dc.contributor.author Esteban, Miguel A.
- dc.date.accessioned 2020-10-22T06:15:32Z
- dc.date.available 2020-10-22T06:15:32Z
- dc.date.issued 2020
- dc.description.abstract Mouse embryonic stem cells cultured with MEK (mitogen-activated protein kinase kinase) and GSK3 (glycogen synthase kinase 3) inhibitors (2i) more closely resemble the inner cell mass of preimplantation blastocysts than those cultured with SL [serum/leukemia inhibitory factor (LIF)]. The transcriptional mechanisms governing this pluripotent ground state are unresolved. Release of promoter-proximal paused RNA polymerase II (Pol2) is a multistep process necessary for pluripotency and cell cycle gene transcription in SL. We show that β-catenin, stabilized by GSK3 inhibition in medium with 2i, supplies transcriptional coregulators 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 proliferation/self-renewal remains tightly controlled by Pol2 pause release under 2i conditions. Our findings explain how pluripotency is reinforced in the ground state and also provide a general model for transcriptional resilience/adaptation upon network perturbation in other contexts.
- dc.format.mimetype application/pdf
- dc.identifier.citation Zhang M, Lai Y, Krupalnik V, Guo P, Guo X, Zhou J et al. β-Catenin safeguards the ground state of mousepluripotency by strengthening the robustness of the transcriptional apparatus. Sci Adv. 2020; 6(29):eaba1593. DOI: 10.1126/sciadv.aba1593
- dc.identifier.doi http://dx.doi.org/10.1126/sciadv.aba1593
- dc.identifier.issn 2375-2548
- dc.identifier.uri http://hdl.handle.net/10230/45551
- dc.language.iso eng
- dc.publisher American Association for the Advancement of Science (AAAS)
- dc.relation.ispartof Sci Adv. 2020; 6(29):eaba1593
- dc.rights Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
- dc.title β-Catenin safeguards the ground state of mousepluripotency by strengthening the robustness of the transcriptional apparatus
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion