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LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [CLIP-seq]

ABSTRACT: LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [CLIP-seq]

PROVIDER: PRJNA689608 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13352896.fastq.gz	Fastqsanger.gz
	SRR13352897.fastq.gz	Fastqsanger.gz

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LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [CLIP-seq]

Project description:LIN28 is an RNA binding protein with important roles in early embryo development by interaction with let-7 microRNA precursors or mRNAs in cytoplasm. Here, we showed novel roles of LIN28 within the nucleolus in cultured pluripotent stem cells (PSCs). We found Lin28 deficiency led to activation of the 2-cell (2C)-like transcriptional program and repression of the ES cell program. Mechanistically, LIN28 maintains a peri-nucleolar heterochromatin-residing complex to repress 2C activator Dux via association with NCL and TRIM28. Meanwhile, it promotes liquid-liquid phase separation (LLPS) of nucleolar proteins FBL and NCL to support nucleolar function through its RNA binding domains and intrinsic disordered regions. These findings elucidate novel roles for nucleolar LIN28 in coordinately regulating the ES/2C state homeostasis, and shed light on RNA binding protein-mediated nucleolar phase separation mechanisms in PSCs and early embryo development.

2021-09-15 | GSE164238 | GEO

LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [Hi-C]

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LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [RNA-seq]

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LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [ChIP-seq]

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LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [ATAC-seq]

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LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [scRNA-seq]

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LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [Hi-C]

Project description:LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [Hi-C]

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LIN28 Promotes Nucleolar/Ribosomal Functions and Phase Separation in Pluripotent Stem Cells

Project description:LIN28 Promotes Nucleolar/Ribosomal Functions and Phase Separation in Pluripotent Stem Cells

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rRNA Biogenesis Regulates Mouse 2C-like State by 3D Structure Reorganization of Peri-Nucleolar Heterochromatin [Hi-C]

Project description:Nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. Its role in regulating stem cell fate is unclear. Here, we present multiple lines of evidence that nucleolar stress induced by interfering rRNA biogenesis can drive two-cell stage embryo-like (2C-like) transcriptional program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells. Mechanistically, the liquid-liquid phase separation (LLPS) mediated by rRNA and nucleolar proteins maintains the formation of peri-nucleolar heterochromatin (PNH). When mES cells undergo rRNA biogenesis defect, the normal LLPS of nucleolus is disrupted, causing deconjugation of NCL/TRIM28 complex on PNH and changes of epigenetic state and 3D structure of PNH, which leads to Dux, a conserved multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals, to be released from the PNH region, activation of 2C-like program and transition of mES cells to 2C-like cells. Embryos with rRNA biogenesis defect are incompatible to develop from 2-cell (2C) to blastocyte (BC) and appear to skew from the blastocyst to earlier cleavage embryo signatures. Our results highlight that nucleolar LLPS-mediated 3D chromatin structure reshaping of PNH compartment regulates the fate transition of mES cells to 2C-like cells. Our findings for the first time elucidate the novel roles of rRNA biogenesis in regulating the 2C-like and ES state homeostasis in cultured cells and suggest that rRNA biogenesis is a new molecular switch from nucleolus-unmatured 2C stage to nucleolus-matured BC stage during murine pre-implantation embryo development.

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rRNA Biogenesis Regulates Mouse 2C-like State by 3D Structure Reorganization of Peri-Nucleolar Heterochromatin [ChIP-seq]

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