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Extensive SUMO modification of chromatin factors distinguishes pluripotent from somatic cells

ABSTRACT: The post-translational modification of proteins by SUMO acts as a key gatekeeper of cell identity. In mouse embryonic fibroblast (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 sets of substrates to preserve the somatic and pluripotent states. Using MS-based proteomics, we show here that the composition of the endogenous SUMOylomes differs dramatically between MEFs and ESCs. In MEFs, SUMOylated proteins organize in a rather diffuse functional network enriched in nuclear factors with general cellular functions. In contrast, in ESCs, SUMOylated proteins form a tightly interconnected network mainly composed of repressive chromatin complexes. We also characterized several SUMOylated pluripotency factors and show that SUMO modification of Dppa2 and Dppa4 hampers their ability to induce a totipotent-like state. Altogether, we propose that rewiring the repertoire of SUMO target networks is a major driver of cell fate transition during embryonic development.

ORGANISM(S): Mus musculus

PROVIDER: GSE144881 | GEO | 2020/09/04

REPOSITORIES: GEO

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Extensive protein group SUMO modification of repressive chromatin factors distinguishes pluripotent from somatic cells

Project description: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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