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Embryonic Stem Cell Differentiation Is Regulated by SET through Interactions with p53 and β-Catenin
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 S...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724474/ https://www.ncbi.nlm.nih.gov/pubmed/33296674 http://dx.doi.org/10.1016/j.stemcr.2020.11.004 |
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author | Harikumar, Arigela Lim, Patrick S.L. Nissim-Rafinia, Malka Park, Jung Eun Sze, Siu Kwan Meshorer, Eran |
author_facet | Harikumar, Arigela Lim, Patrick S.L. Nissim-Rafinia, Malka Park, Jung Eun Sze, Siu Kwan Meshorer, Eran |
author_sort | Harikumar, Arigela |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7724474 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-77244742020-12-13 Embryonic Stem Cell Differentiation Is Regulated by SET through Interactions with p53 and β-Catenin Harikumar, Arigela Lim, Patrick S.L. Nissim-Rafinia, Malka Park, Jung Eun Sze, Siu Kwan Meshorer, Eran Stem Cell Reports Article 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. Elsevier 2020-12-08 /pmc/articles/PMC7724474/ /pubmed/33296674 http://dx.doi.org/10.1016/j.stemcr.2020.11.004 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Harikumar, Arigela Lim, Patrick S.L. Nissim-Rafinia, Malka Park, Jung Eun Sze, Siu Kwan Meshorer, Eran Embryonic Stem Cell Differentiation Is Regulated by SET through Interactions with p53 and β-Catenin |
title | Embryonic Stem Cell Differentiation Is Regulated by SET through Interactions with p53 and β-Catenin |
title_full | Embryonic Stem Cell Differentiation Is Regulated by SET through Interactions with p53 and β-Catenin |
title_fullStr | Embryonic Stem Cell Differentiation Is Regulated by SET through Interactions with p53 and β-Catenin |
title_full_unstemmed | Embryonic Stem Cell Differentiation Is Regulated by SET through Interactions with p53 and β-Catenin |
title_short | Embryonic Stem Cell Differentiation Is Regulated by SET through Interactions with p53 and β-Catenin |
title_sort | embryonic stem cell differentiation is regulated by set through interactions with p53 and β-catenin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724474/ https://www.ncbi.nlm.nih.gov/pubmed/33296674 http://dx.doi.org/10.1016/j.stemcr.2020.11.004 |
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