β-Catenin safeguards the ground state of mouse pluripotency by strengthening the robustness of the transcriptional apparatus
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β-Catenin safeguards the ground state of mouse pluripotency by strengthening the robustness of the transcriptional apparatus. / Zhang, Meng; Lai, Yiwei; Krupalnik, Vladislav; Guo, Pengcheng; Guo, Xiangpeng; Zhou, Jianguo; Xu, Yan; Yu, Zhijun; Liu, Longqi; Jiang, Ao; Li, Wenjuan; Abdul, Mazid Md; Ma, Gang; Li, Na; Fu, Xiuling; Lv, Yuan; Jiang, Mengling; Tariq, Muqddas; Kanwal, Shahzina; Liu, Hao; Xu, Xueting; Zhang, Hui; Huang, Yinghua; Wang, Lulu; Chen, Shuhan; Babarinde, Isaac A.; Luo, Zhiwei; Wang, Dongye; Zhou, Tiantian; Ward, Carl; He, Minghui; Ibañez, David P.; Li, Yunpan; Zhou, Jiajian; Yuan, Jie; Feng, Yayan; Arumugam, Karthik; Di Vicino, Umberto; Bao, Xichen; Wu, Guangming; Schambach, Axel; Wang, Huating; Sun, Hao; Gao, Fei; Qin, Baoming; Hutchins, Andrew P.; Doble, Bradley W.; Hartmann, Christine; Cosma, Maria Pia; Qin, Yan; Xu, Guo Liang; Chen, Runsheng; Volpe, Giacomo; Chen, Liang; Hanna, Jacob H.; Esteban, Miguel A.
In: Science Advances, Vol. 6, No. 29, eaba1593, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - β-Catenin safeguards the ground state of mouse pluripotency by strengthening the robustness of the transcriptional apparatus
AU - Zhang, Meng
AU - Lai, Yiwei
AU - Krupalnik, Vladislav
AU - Guo, Pengcheng
AU - Guo, Xiangpeng
AU - Zhou, Jianguo
AU - Xu, Yan
AU - Yu, Zhijun
AU - Liu, Longqi
AU - Jiang, Ao
AU - Li, Wenjuan
AU - Abdul, Mazid Md
AU - Ma, Gang
AU - Li, Na
AU - Fu, Xiuling
AU - Lv, Yuan
AU - Jiang, Mengling
AU - Tariq, Muqddas
AU - Kanwal, Shahzina
AU - Liu, Hao
AU - Xu, Xueting
AU - Zhang, Hui
AU - Huang, Yinghua
AU - Wang, Lulu
AU - Chen, Shuhan
AU - Babarinde, Isaac A.
AU - Luo, Zhiwei
AU - Wang, Dongye
AU - Zhou, Tiantian
AU - Ward, Carl
AU - He, Minghui
AU - Ibañez, David P.
AU - Li, Yunpan
AU - Zhou, Jiajian
AU - Yuan, Jie
AU - Feng, Yayan
AU - Arumugam, Karthik
AU - Di Vicino, Umberto
AU - Bao, Xichen
AU - Wu, Guangming
AU - Schambach, Axel
AU - Wang, Huating
AU - Sun, Hao
AU - Gao, Fei
AU - Qin, Baoming
AU - Hutchins, Andrew P.
AU - Doble, Bradley W.
AU - Hartmann, Christine
AU - Cosma, Maria Pia
AU - Qin, Yan
AU - Xu, Guo Liang
AU - Chen, Runsheng
AU - Volpe, Giacomo
AU - Chen, Liang
AU - Hanna, Jacob H.
AU - Esteban, Miguel A.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1126/sciadv.aba1593
DO - 10.1126/sciadv.aba1593
M3 - Journal article
C2 - 32832621
AN - SCOPUS:85090069337
VL - 6
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 29
M1 - eaba1593
ER -
ID: 248461817