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DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [RNA-seq]

ABSTRACT: Pluripotent stem cells are unique in their large nucleus and manifestly open chromatin structure with hypertranscriptional activities. How the nucleolus, the largest membraneless and phase-separated subnuclear organelle, maintains its structural integrity in pluripotency maintenance remains incompletely understood. By studying nucleolus-specific DEAD-box RNA helicase-18 (DDX18) in human embryonic stem cells, we discover mechanisms controlling nucleolus phase separation and chromatin organization.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182802 | GEO | 2024/11/07

REPOSITORIES: GEO

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DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [DDX18_iCLIP-seq]

Project description:Pluripotent stem cells are unique in their large nucleus and manifestly open chromatin structure with hypertranscriptional activities. How the nucleolus, the largest membraneless and phase-separated subnuclear organelle, maintains its structural integrity in pluripotency maintenance remains incompletely understood. By studying nucleolus-specific DEAD-box RNA helicase-18 (DDX18) in human embryonic stem cells, we discover mechanisms controlling nucleolus phase separation and chromatin organization.

2024-11-07 | GSE182801 | GEO

DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [DDX18_CHIP-seq]

2024-11-07 | GSE182800 | GEO

DDX18 safeguards rDNA epigenetic landscape by counteracting PRC2 and maintains ESC identity

Project description:Here we have RNA binding protein DDX18 connecting rRNA transcription to early embryo development and embryonic stem cell (ESC) identity maintenance. DDX18 mutant embryos suffer lethality during preimplantation development. DDX18 depletion impairs ESC self-renewal and pluripotency, which phenotype-copies RNA polymerase I (RNAPI) inhibition. Mechanistically, DDX18 is recruited to rDNA by RNAPI transcription machinery and senses rRNA transcription by binding to pre-rRNA. In nucleolus, DDX18 surrounds DFC ring and interacts with PRC2. In the presence of transcribed pre-rRNA, DDX18 interaction with PRC2 makes EZH2 unstably binding to the other components of PRC2, thereby preventing PRC2 engagement and counteracting H3K27me3 mediated silencing at rDNA chromatin. Together, our study shows that DDX18 plays important roles in safeguarding ESCs identity through regulating epigenetic states of rDNA locus and maintaining euchromatin structure in nucleolus.

2019-12-25 | GSE124580 | GEO

Effects of DDX18 on chromatin characteristics

Project description:Hs766T cell line of pancreatic ductal adenocarcinoma (PDAC) highly expressed DDX18, and the effects of DDX18 on chromatin characteristics of PDAC cells were examined

2024-07-03 | GSE241163 | GEO

DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells.

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-11-07 | GSE182804 | GEO

HP1β dependent phase separation regulates embryonic stem cells exit from naïve pluripotent state

Project description:Liquid-liquid phase separation has drawn great attention as a physical process that mediates the formation of membraneless organelles in cells to coordinate biological reactions in space and time. Previously, it was proposed that the formation of phase-separated droplets is a unique property of HP1α. Here, we show that HP1β, but not HP1α and HP1ɤ, forms nucleosome dependent phase separated droplets. We demonstrate that H3K9me3 is required for HP1β dependent phase separation. Importantly, HP1β dependent phase separation regulates heterochromatin formation, thus controlling embryonic stem cells differentiation. In response to pluripotency exit, HP1β is phosphorylated at serine 89 recruiting KAP1, a pluripotency regulator, and sequestering it in the heterochromatin compartment. This induces changes in the level of pluripotency factors and triggers pluripotency exit. We propose that such a trapping mechanism creates a fast and dynamic mode of remote control of gene expression to regulate cell fate decisions solely based on membraneless organelles.

2022-05-01 | E-MTAB-8329 | biostudies-arrayexpress

Mapping nucleolus-associated chromatin interactions by nucleolus-Hi-C reveals repression network

Project description:Nucleolus plays a key role in organizing global nuclear structure and facilitating gene regulation, but the three dimensional information within the nucleolus associated chromatins are still unknown, so here we development the Nucleolus Hi-C (NHi-C) experimental technique, which combines the nucleolus isolation with Hi-C experiment, and study the interactions within and surrounding nucleolus in human cells with a high resolution. With NHi-C experiment, we report how the nucleolus-associated chromatin regions interact at genome scale, and how these interactions organize the repressive nucleus architecture.

2021-02-01 | GSE90003 | GEO

RNA-seq analysis in triple negative breast cancer cells after knocking down DDX18

Project description:To assess the function of DDX18 in TNBCs, we performed transcriptome analysis through high-throughput RNA-Seq of control and DDX18 knockdown cells

2022-07-13 | GSE207869 | GEO

The influence of DDX18 high expression in PDAC cells Hs766T on the expression of other intracellular molecules

Project description:DDX18 promotes the occurrence and development of pancreatic cancer and the maintenance of stem cell characteristics, but the mechanism through which these effects are accomplished is still unclear. The purpose of this sequencing is to screen the differential genes affected by DDX18 expression

2024-07-03 | GSE241328 | GEO

Mapping of nucleolus-associated chromosomal domains during replicative senescence.

Project description:Nucleolus-associated DNA was isolated from cross-linked proliferating and senescent IMR90 human fibroblasts and hybridized against genomic (1) or non-nucleolar (2) DNA to map nucleolus-associated chromosomal domains.

2017-06-18 | GSE78043 | GEO

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