Exploration of nuclear body-enhanced sumoylation reveals that PML represses 2-cell features of embryonic stem cells
Tessier, Sarah; Ferhi, Omar; Geoffroy, Marie-Claude; González Prieto, Román; Canat, Antoine; Quentin, Samuel; Pla, Marika; Niwa-Kawakita, Michiko; Bercier, Pierre; Rerolle, Domitille; Therizols, Pierre; Fabre, Emmanuelle; Vertegaal, Alfred C. O.; de Thé,
- Published
- 2022
- Publisher
- Springer Nature
- Language
- en
Abstract
Membrane-less organelles are condensates formed by phase separation whose functions often remain enigmatic. Upon oxidative stress, PML scaffolds Nuclear Bodies (NBs) to regulate senescence or metabolic adaptation. PML NBs recruit many partner proteins, but the actual biochemical mechanism underlying their pleiotropic functions remains elusive. Similarly, PML role in embryonic stem cell (ESC) and retro-element biology is unsettled. Here we demonstrate that PML is essential for oxidative stress-driven partner SUMO2/3 conjugation in mouse ESCs (mESCs) or leukemia, a process often followed by their poly-ubiquitination and degradation. Functionally, PML is required for stress responses in mESCs. Differential proteomics unravel the KAP1 complex as a PML NB-dependent SUMO2-target in arsenic-treated APL mice or mESCs. PML-driven KAP1 sumoylation enables activation of this key epigenetic repressor implicated in retro-element silencing. Accordingly, Pml−/− mESCs re-express transposable elements and display 2-Cell-Like features, the latter enforced by PML-controlled SUMO2-conjugation of DPPA2. Thus, PML orchestrates mESC state by coordinating SUMO2-conjugation of different transcriptional regulators, raising new hypotheses about PML roles in cancer.
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Corrections&amendments Author Correction: Exploration of nuclear body-enhanced sumoylation reveals that PML represses 2-cell features of embryonic stem cells Sarah Tessier ,OmarFerhi,Marie-ClaudeGeoffroy , Román González-Prieto , Antoine Canat ,SamuelQuentin,MarikaPla,MichikoNiwa-Kawakita , Pierre Bercier, Domitille Rérolle, Marilyn Tirard, Pierre Therizols , Emmanuelle Fabre ,AlfredC.O.Vertegaal,HuguesdeThé & Valérie Lallemand-Breitenbach Marylin Tirard, who generated the His 6 -HA-Sumo1 knock-in model, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article. Additionally, the following was added to the Author Contributions: “M.T. generated the His 6 -HA-Sumo1 Knock-in model28.” Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2023 Correction to: Nature Communications https://doi.org/10.1038/s41467-022-33147-6, published online 29 September 2022 https://doi.org/10.1038/s41467-022-35750-z Check for updates nature communications (2023) 14:124 | 1 1234567890():,; 1234567890():,;
