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SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE135451 | GEO | 2021/05/18

REPOSITORIES: GEO

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SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation [RNA-Seq]

Project description:The transition from pluripotent to somatic states marks a critical checkpoint in mammalian development. How this is regulated remains largely unresolved. Here we report the identification of SS18 by whole genome CRISPR screen as a checkpoint regulator. SS18 regulates pluripotent to somatic transition or PST by relocating from pluripotent loci to somatic ones accompanied by corresponding chromatin closing-opening and remodeling of SS18-centric protein complexes. Mechanistically, SS18 forms phase separation granules (PSG) with an intrinsically disordered region (IDR) rich in tyrosine (Y), which, once mutated, no longer form PSG nor rescue SS18-/- defect in PST. These results reveal that rapid cell fate decision can be achieved by massive redistribution of chromatin remodeling37 complexes through phase separation.

2021-05-18 | GSE135397 | GEO

SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation [ATAC-Seq]

2021-05-18 | GSE135395 | GEO

SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation [ChIP-Seq Dataset 1]

2021-05-18 | GSE135396 | GEO

SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation [ChIP-Seq Dataset 2]

2021-05-18 | GSE152175 | GEO

SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation [ChIP-Seq Dataset 3]

2021-05-31 | GSE175818 | GEO

SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation

Project description:SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation

| PRJNA558951 | ENA

SS18 regulates pluripotent-somatic transition through phase separation.

Project description:The transition from pluripotent to somatic states marks a critical event in mammalian development, but remains largely unresolved. Here we report the identification of SS18 as a regulator for pluripotent to somatic transition or PST by CRISPR-based whole genome screens. Mechanistically, SS18 forms microscopic condensates in nuclei through a C-terminal intrinsically disordered region (IDR) rich in tyrosine, which, once mutated, no longer form condensates nor rescue SS18-/- defect in PST. Yet, the IDR alone is not sufficient to rescue the defect even though it can form condensates indistinguishable from the wild type protein. We further show that its N-terminal 70aa is required for PST by interacting with the Brg/Brahma-associated factor (BAF) complex, and remains functional even swapped onto unrelated IDRs or even an artificial 24 tyrosine polypeptide. Finally, we show that SS18 mediates BAF assembly through phase separation to regulate PST. These studies suggest that SS18 plays a role in the pluripotent to somatic interface and undergoes liquid-liquid phase separation through a unique tyrosine-based mechanism.

| S-EPMC8253816 | biostudies-literature

SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation [RNA-Seq]

Project description:SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation [RNA-Seq]

| PRJNA558755 | ENA

SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation [ATAC-Seq]

Project description:SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation [ATAC-Seq]

| PRJNA558751 | ENA

SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation [ChIP-Seq Dataset 3]

Project description:SS18 is a phase-separation protein relocating from pluripotent to somatic loci during mESC differentiation [ChIP-Seq Dataset 3]

| PRJNA733822 | ENA

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