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

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

PROVIDER: PRJNA512533 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8385540_1.fastq.gz	Fastqsanger.gz
	SRR8385540_2.fastq.gz	Fastqsanger.gz
	SRR8385550_1.fastq.gz	Fastqsanger.gz
	SRR8385550_2.fastq.gz	Fastqsanger.gz
	SRR8385560_1.fastq.gz	Fastqsanger.gz

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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

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

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Effects of DDX18 on chromatin characteristics

Project description:Effects of DDX18 on chromatin characteristics

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The Elongation Factor and Histone Chaperone Spt6 Maintains ESC Pluripotency by Controlling Super-Enhancers and Counteracting Polycomb Repressive Complex 2

Project description:Spt6 coordinates nucleosome dis- and re-assembly, transcriptional elongation and mRNA processing. Here, we report that depleting Spt6 in ESCs reduced expression of pluripotency factors, increased expression of cell lineage-affiliated developmental regulators, and induced cell morphological and biochemical changes indicative of ESC differentiation. Selective down-regulation of pluripotency factors upon Spt6 depletion may be mechanistically explained by its enrichment at ESC super-enhancers where Spt6 controlled H3K27 acetylation and methylation, and super-enhancer RNA transcription. In ESCs, Spt6 interacted with the PRC2 core subunit Suz12 and prevented H3K27me3 accumulation at ESC super-enhancers and associated promoters. Biochemical as well as functional experiments revealed that Spt6 could compete for binding of the PRC2 methyltransferase Ezh2 to Suz12 and reduce PRC2 chromatin engagement. Thus, in addition to serving as histone chaperone and transcription elongation factor, Spt6 counteracts repression by opposing H3K27me3 deposition at critical genomic regulatory regions.

2017-09-01 | GSE103180 | GEO

EZH1 in germ cells safeguards the function of PRC2 during spermatogenesis.

Project description:We previously reported the requirement of Polycomb Repressive Complex 2 (PRC2) for spermatogenesis through transcriptional repression of somatic genes and meiosis-specific genes. To characterize how PRC2's two methyltransferase subunits, EZH1 and EZH2, regulate histone H3 lysine 27 (H3K27) methylation during germ cell development, we generated mouse models with a germline ablation of EZH1 and/or EHZ2. Only the combined loss of EZH1 and EZH2 caused a depletion of global H3K27me3 marks and meiotic arrest in spermatocytes. Genome-wide analysis of H3K27me3 in spermatogenic cells revealed that a noncanonical EZH1-PRC2 could establish and maintain this histone mark on somatic genes and certain meiotic genes. Consistent with it having active enhancers in testis, Ezh1 was not only abundant in highly differentiated spermatocytes but also in actively proliferating progenitor and stem germ cells. Taken together, our findings suggest that the expression level of Ezh1 determines the restoration of H3K27 methylation in the absence of the canonical EZH2-PRC2.

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Project description:PRC2 profile and chromatin marks in ESC and NPC

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ZFP462 safeguards neural lineage specification by targeting G9A/GLP-mediated heterochromatin to silence enhancers

Project description:ZNF462 haploinsufficiency is linked to Weiss-Kruszka Syndrome, a genetic disorder characterized by neurodevelopmental defects including Autism. Though conserved in vertebrates and essential for embryonic development the molecular functions of ZNF462 remain unclear. We identified its murine homolog ZFP462 in a screen for mediators of epigenetic gene silencing. Here, we show that ZFP462 safeguards neural lineage specification of mouse embryonic stem cells (ESCs) by targeting the H3K9-specific histone methyltransferase complex G9A/GLP to silence mesoendodermal genes. ZFP462 binds to transposable elements (TEs) that are potential enhancers harboring ESC-specific transcription factor (TF) binding sites. Recruiting G9A/GLP, ZFP462 seeds heterochromatin, restricting TF binding. Loss of ZFP462 in ESCs results in increased chromatin accessibility at target sites and ectopic expression of mesoendodermal genes. Taken together, ZFP462 confers lineage- and locus-specificity to the broadly expressed epigenetic regulator G9A/GLP. Our results suggest that aberrant activation of lineage non-specific genes in the neuronal lineage underlies ZNF462-associated neurodevelopmental pathology.

2023-05-10 | PXD037238 | Pride

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

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.

2024-11-13 | GSE182855 | GEO

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