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Title: Embryonic stem cell differentiation is regulated by SET through interactions with p53 and β-Catenin
Authors: Harikumar, Arigela
Lim, Patrick S. L.
Nissim-Rafinia, Malka
Park, Jung Eun
Sze, Siu Kwan
Meshorer, Eran
Keywords: Science::Biological sciences
Issue Date: 2020
Source: Harikumar, A., Lim, P. S. L., Nissim-Rafinia, M., Park, J. E., Sze, S. K. & Meshorer, E. (2020). Embryonic stem cell differentiation is regulated by SET through interactions with p53 and β-Catenin. Stem Cell Reports, 15(6), 1260-1274.
Journal: Stem Cell Reports 
Abstract: The multifunctional histone chaperone, SET, is essential for embryonic development in the mouse. Previously, we identified SET as a factor that is rapidly downregulated during embryonic stem cell (ESC) differentiation, suggesting a possible role in the maintenance of pluripotency. Here, we explore SET's function in early differentiation. Using immunoprecipitation coupled with protein quantitation by LC-MS/MS, we uncover factors and complexes, including P53 and β-catenin, by which SET regulates lineage specification. Knockdown for P53 in SET-knockout (KO) ESCs partially rescues lineage marker misregulation during differentiation. Paradoxically, SET-KO ESCs show increased expression of several Wnt target genes despite reduced levels of active β-catenin. Further analysis of RNA sequencing datasets hints at a co-regulatory relationship between SET and TCF proteins, terminal effectors of Wnt signaling. Overall, we discover a role for both P53 and β-catenin in SET-regulated early differentiation and raise a hypothesis for SET function at the β-catenin-TCF regulatory axis.
ISSN: 2213-6711
DOI: 10.1016/j.stemcr.2020.11.004
Rights: © 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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