Proteomics

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Extensive protein group SUMO modification of repressive chromatin factors distinguishes pluripotent from somatic cells (total proteome)


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.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryo, Stem Cell, Fibroblast

SUBMITTER: Ivo Hendriks  

LAB HEAD: Michael Lund Nielsen

PROVIDER: PXD020287 | Pride | 2020-09-16

REPOSITORIES: Pride

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Publications

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

Theurillat Ilan I   Hendriks Ivo A IA   Cossec Jack-Christophe JC   Andrieux Alexandra A   Nielsen Michael L ML   Dejean Anne A  

Cell reports 20200901 11


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 protei  ...[more]

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