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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE135395 | 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.

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