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Nanog safeguards early embryogenesis against global activation of maternal β-catenin activity by interfering with TCF factors

He M, Zhang R, Zhang F, Jiao S, Ye D, Wang H, Sun Y
bioRxiv. 2019;[preprint] doi:/10.1101/821702
Maternal β-catenin activity is essential and critical for dorsal induction and its dorsal activation has been thoroughly studied. However, how the maternal β-catenin activity is suppressed in the non-dorsal cells remains poorly understood. Nanog is known to play a central role for maintenance of the pluripotency and maternal-to-zygotic transition. Here we reveal a novel role of Nanog as a strong repressor of maternal Wnt/β-catenin signaling to safeguard the embryo against hyper-activation of maternal β-catenin activity and hyper-dorsalization. Knockdown of nanog at different levels led to either posteriorization or dorsalization, mimicking zygotic or maternal activation of Wnt/β-catenin activities, and the maternal-zygotic mutant of nanog (MZnanog) showed strong activation of maternal β-catenin and hyper-dorsalization. Although a constitutive-activator-type Nanog (Vp16-Nanog, lacking the N-terminal) perfectly rescued the defects of maternal to zygotic transition in MZnanog, it did not rescue the phenotypes resulting from β-catenin activation. Mechanistically, the N-terminal of Nanog directly interacts with TCF and interferes with the binding of β-catenin to TCF, thereby attenuating the transcriptional activity of β-catenin. Therefore, our study establishes a novel role for Nanog in repressing maternal β-catenin activity and demonstrates a transcriptional switch between β-catenin/TCF and Nanog/TCF complexes, which safeguards the embryo from global activation of maternal β-catenin activity.
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