Extensive SUMO Modification of Repressive Chromatin Factors Distinguishes Pluripotent from Somatic Cells - Institut Pasteur Access content directly
Journal Articles Cell Reports Year : 2020

Extensive SUMO Modification of Repressive Chromatin Factors Distinguishes Pluripotent from Somatic Cells

Abstract

Post-translational modification by SUMO is a key regulator of cell identity. In mouse embryonic fibroblasts (MEFs), SUMO impedes reprogramming to pluripotency, while in embryonic stem cells (ESCs), it represses the emergence of totipotent-like cells, suggesting that SUMO targets distinct substrates to preserve somatic and pluripotent states. Using MS-based proteomics, we show that the composition of endogenous SUMOylomes differs dramatically between MEFs and ESCs. In MEFs, SUMO2/3 targets proteins associated with canonical SUMO functions, such as splicing, and transcriptional regulators driving somatic enhancer selection. In contrast, in ESCs, SUMO2/3 primarily modifies highly interconnected repressive chromatin complexes, thereby preventing chromatin opening and transitioning to totipotent-like states. We also characterize several SUMO-modified pluripotency factors and show that SUMOylation of Dppa2 and Dppa4 impedes the conversion to 2-cell-embryo-like states. Altogether, we propose that rewiring the repertoire of SUMO target networks is a major driver of cell fate decision during embryonic development.
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pasteur-03234751 , version 1 (25-05-2021)

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Ilan Theurillat, Ivo Hendriks, Jack-Christophe Cossec, Alexandra Andrieux, Michael Nielsen, et al.. Extensive SUMO Modification of Repressive Chromatin Factors Distinguishes Pluripotent from Somatic Cells. Cell Reports, 2020, 32 (11), pp.108146. ⟨10.1016/j.celrep.2020.108146⟩. ⟨pasteur-03234751⟩
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