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

Identificadores del recurso

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

2375-2548

http://hdl.handle.net/10230/45551

http://dx.doi.org/10.1126/sciadv.aba1593

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(e-Repositori: Repositori digital de la UPF)

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Title:: β-Catenin safeguards the ground state of mousepluripotency by strengthening the robustness of the transcriptional apparatus
Description:: 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.
Idioma:: English
Relation:: Sci Adv. 2020; 6(29):eaba1593
Autor/Productor:: Zhang, Meng; Arumugam, Karthik; Di Vicino, Umberto; Cosma, Maria Pia, 1970-; Esteban, Miguel A.
Publisher:: American Association for the Advancement of Science (AAAS)
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).; https://creativecommons.org/licenses/by-nc/4.0/; info:eu-repo/semantics/openAccess
Date:: 2020
Tipo de recurso:: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion
Format:: application/pdf

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3. <element name="others">
  1. <field name="handle">10230/45551</field>
  2. <field name="identifier">oai:repositori.upf.edu:10230/45551</field>
  3. <field name="lastModifyDate">2020-10-23 03:30:22.618</field>
  </element>
4. <element name="repository">
  1. <field name="name">Repositori digital de la UPF</field>
  2. <field name="mail">repositori@upf.edu</field>
  </element>
</metadata>