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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 (total proteome)

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.

2020-09-16 | PXD020287 | Pride

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

2020-09-16 | PXD017697 | Pride

Genome wide occupancy of SUMO machinery in proliferative and Ras-induced senescent human primary fibroblasts

Project description:Transcription factors represent one of the largest groups of proteins regulated by SUMO, and their modification has generally been correlated with transcriptional repression. However, as most of the studies focus on specific sumoylated transcriptional regulators, the distribution and global role of SUMO on chromatin in relation to transcription regulation remain largely unknown. To investigate this role, we determined the occupancy of SUMO machinery proteins on chromatin by ChIP coupled to sequencing in human primary cells. Examination of 3 histone modifications, Polymerase II, SUMO1, SUMO2, Ubc9 and PIASy in proliferative and Ras-induced senescent fibroblasts.

2013-07-24 | E-GEOD-42211 | biostudies-arrayexpress

Genome wide occupancy of SUMO machinery in proliferative and Ras-induced senescent human primary fibroblasts

2013-07-24 | GSE42211 | GEO

A SUMOylation-induced Satb1/Satb2 switch drives embryonic stem cell differentiation [HiC]

Project description:The chromatin organizers Satb1 and Satb2 regulate developmental genes in a tissue- and locus-specific manner. In mouse Embryonic Stem Cells (mESCs), the Satb proteins are involved in the balance between pluripotency and differentiation by direct control of key developmental factors such as Nanog and a number of Hox genes. Despite their structural similarities, the Satb proteins regulate mESC pluripotency in opposing ways: Satb1 promotes differentiation by repressing Nanog and activating the neural genes Bcl2 and Nestin, while Satb2 supports the pluripotent state by activating Nanog and repressing Satb1. To further address the mechanisms by which the Satb proteins regulate gene expression, we examined the conjugation of Satb2 with the small ubiquitin-like modifier (SUMO) in pluripotent and differentiated mESCs. We describe for the first time the endogenous SUMOylation of Satb2 in mESCs as a response to developmental cues. We found that Satb2 is progressively SUMO2-modified during differentiation of ESCs towards ectodermal precursors. Moreover, we identified Zfp451 as a SUMO E3 ligase able to interact with and modify Satb2 with SUMO2 in vitro and in vivo. Ablation of Zfp451 or mutation of the SUMO-acceptor lysines in the Satb2 protein disrupt the ability of mESCs to efficiently shut-down pluripotency genes and activate the differentiation program. Importantly, forced expression of SUMO2-Satb2 N-terminal fusions rescues the differentiation defect of SUMO-Satb2 deficient mESCs. Mechanistically, SUMOylation reduces binding of Satb2 to a subset of loci associated to pluripotency genes and changes the composition of Satb2-containing complexes in chromatin. Taken together, our data suggests that SUMO modification of the chromatin organizer Satb2 by the E3 ligase Zfp451 is required for the efficient downregulation of pluripotency genes and initiation of the differentiation program in mouse embryonic stem cells.

2021-07-08 | GSE153078 | GEO

A SUMOylation-induced Satb1/Satb2 switch drives embryonic stem cell differentiation [RNA-Seq]

2021-07-08 | GSE119990 | GEO

A SUMOylation-induced Satb1/Satb2 switch drives embryonic stem cell differentiation [ChIP-Seq]

2021-07-08 | GSE119989 | GEO

Chromatin landscapes in mouse haploid stem cells [RRBS-seq]

Project description:We generate histone modification profiles and DNA methylation profiles of mouse haploid embryonic stem cells. By comparison to mouse diploid ESCs and MEFs, we found the similar chromatin landscapes between haESCs and mESCs, which reveal the self-renew ability and pluripotency in haESCs. Besides, haESCs specific chromatin landscapes show its sperm-like functions.

2018-03-07 | GSE107359 | GEO

Chromatin landscapes in mouse haploid stem cells [ChIP-seq]

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Genome-wide Dppa4 binding in E14 mESC, 3T3, and P19 cells

Project description:DPPA4 is a DNA-associated factor that is highly and selectively expressed in embryonic stem cells. DPPA4 expression is strikingly downregulated upon loss of pluripotency, but is reactivated in a number of cancer cell types. It has recently been identified as an oncogene and shown to promote cell proliferation and anchorage independent growth; Dppa4-transformed cells can form tumors in vivo in mice. DPPA4 has been shown to associate with active chromatin and histone H3, but the global binding dynamics of DPPA4 are unknown. Additionally, only several DPPA4 gene targets are known. To better understand the role of DPPA4 in embryonic stem cell pluripotency and oncogenesis, we performed ChIP-Seq in E14 mouse embryonic stem cells (mESC), 3T3 cells ectopically expressing DPPA4, and P19 embryonic carcinoma cells.

2018-08-07 | GSE95055 | GEO

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