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EZH2 Reduction Is an Essential Mechanoresponse for the Maintenance of Super-enhancer Polarization

ABSTRACT: EZH2 Reduction Is an Essential Mechanoresponse for the Maintenance of Super-enhancer Polarization

PROVIDER: PRJNA429827 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6470156_1.fastq.gz	Fastqsanger.gz
	SRR6470156_2.fastq.gz	Fastqsanger.gz
	SRR6470157_1.fastq.gz	Fastqsanger.gz
	SRR6470157_2.fastq.gz	Fastqsanger.gz
	SRR6470158_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

EZH2 Reduction Is an Essential Mechanoresponse for the Maintenance of Super-enhancer Polarization

Project description:Despite the ubiquitous mechanical cues at both spatial and temporal dimensions, cell identities and functions are largely immune to the everchanging mechanical stimuli. To understand the molecular basis of this epigenetic stability, we interrogated compressive force elicited transcriptomic changes in mesenchymal stem cells purified from human periodontal ligament (PDLSCs), and identified H3K27me3 and E2F signatures populated within up- and weakly down-regulated genes respectively. Consistently, expressions of several E2F family transcription factors and EZH2, as core methyltransferase for H3K27me3, decreased in response to mechanical stress, which were attributed to force induced redistribution of RB from nucleoplasm to lamina. Importantly, although epigenomic analysis on H3K27me3 landscape only demonstrated correlating changes at one group of mechanoresponsive genes, we observed a genome-wide destabilization of super-enhancers along with aberrant EZH2 retention. These super-enhancers were tightly bounded by H3K27me3 domain on one side and exhibited attenuating H3K27ac deposition and flattening H3K27ac peaks after force exposure, analogous to increased H3K27ac entropy or decreased H3K27ac polarization. Interference of force induced EZH2 reduction could drive nuclear actin filaments dependent collision between EZH2 and super-enhancers and functionally compromise the multipotency of PDLSC following mechanical stress. These findings together unveil a specific contribution of EZH2 reduction for maintenance of super-enhancer stability and cell identity in mechanoresponse.

2020-09-23 | GSE109167 | GEO

EZH2 Reduction Is an Essential Mechanoresponse for the Maintenance of Super-enhancer Polarization

2020-09-23 | GSE109166 | GEO

EZH2 Reduction Is an Essential Mechanoresponse for the Maintenance of Super-enhancer Polarization

Project description:EZH2 Reduction Is an Essential Mechanoresponse for the Maintenance of Super-enhancer Polarization

| PRJNA429832 | ENA

EZH2 Reduction Is an Essential Mechanoresponse for the Maintenance of Super-enhancer Polarization

Project description:EZH2 Reduction Is an Essential Mechanoresponse for the Maintenance of Super-enhancer Polarization

| PRJNA429831 | ENA

EZH2 Reduction Is an Essential Mechanoresponse for the Maintenance of Super-enhancer Polarization

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

2020-09-23 | GSE109168 | GEO

EZH2 reduction is an essential mechanoresponse for the maintenance of super-enhancer polarization against compressive stress in human periodontal ligament stem cells.

Project description:Despite the ubiquitous mechanical cues at both spatial and temporal dimensions, cell identities and functions are largely immune to the everchanging mechanical stimuli. To understand the molecular basis of this epigenetic stability, we interrogated compressive force-elicited transcriptomic changes in mesenchymal stem cells purified from human periodontal ligament (PDLSCs), and identified H3K27me3 and E2F signatures populated within upregulated and weakly downregulated genes, respectively. Consistently, expressions of several E2F family transcription factors and EZH2, as core methyltransferase for H3K27me3, decreased in response to mechanical stress, which were attributed to force-induced redistribution of RB from nucleoplasm to lamina. Importantly, although epigenomic analysis on H3K27me3 landscape only demonstrated correlating changes at one group of mechanoresponsive genes, we observed a genome-wide destabilization of super-enhancers along with aberrant EZH2 retention. These super-enhancers were tightly bounded by H3K27me3 domain on one side and exhibited attenuating H3K27ac deposition and flattening H3K27ac peaks along with compensated EZH2 expression after force exposure, analogous to increased H3K27ac entropy or decreased H3K27ac polarization. Interference of force-induced EZH2 reduction could drive actin filaments dependent spatial overlap between EZH2 and super-enhancers and functionally compromise the multipotency of PDLSC following mechanical stress. These findings together unveil a specific contribution of EZH2 reduction for the maintenance of super-enhancer stability and cell identity in mechanoresponse.

| S-EPMC7493952 | biostudies-literature

Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth [ATAC-seq]

Project description:Human silencers have been shown to exist and regulate developmental gene expression. However, the functional importance of human silencers needs to be elucidated, such as whether they can form “super-silencers” and whether they are linked to cancer progression. Here, through interrogating two putative silencer components of FGF18 gene, we found that two nearby silencers can cooperate via compensatory chromatin interactions to form a “super-silencer”. Furthermore, double knockout of two silencers exhibited synergistic upregulation of FGF18 expression and changes of cell identity. To perturb the “super-silencers”, we applied combinational treatment of an EZH2 inhibitor GSK343, and a REST inhibitor, X5050 (“GR”). We found that GR led to severe loss of TADs and loops, while the use of one inhibitor by itself only showed mild changes. Such changes in TADs and loops were associated with reduced CTCF and TOP2A mRNA levels. Moreover, GSK343 and X5050 synergistically upregulated super-silencer-controlled genes related to cell cycle, apoptosis and DNA damage, leading to anticancer effects both in vitro and in vivo. Overall, our data demonstrated the first example of a “super-silencer” and showed that combinational usage of GSK343 and X5050 to disrupt “super-silencers” could potentially lead to cancer ablation.

2024-05-08 | GSE239323 | GEO

Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth [Cut&Run]

2024-05-08 | GSE239324 | GEO

Epigenetic Maintenance of Stemness and Malignancy in Peripheral Neuroectodermal Tumors by EZH2

Project description:Chromatin modifications are increasingly recognized as a key mechanism in cancer. The histone methyl-transferase Enhancer of Zeste, Drosophila, Homolog 2 (EZH2) is the enzymatic subunit of the polycomb PRC2 complex and methylates histone H3K27, thereby, mediating gene silencing. Down-regulation of EZH2 by RNA interference in ET suppressed oncogenic transformation, tumor development and metastasis in a respective mouse model. Further microarray analysis of EZH2 knock down, or functionally linked HDAC-inhibitor treatment revealed an undifferentiated reversible phenotype in ET maintained by EZH2. EZH2 suppression resulted in a generalized loss of H3K27me3 as well as an increase in H3 acetylation levels. In addition, ChIP-Chip assays for H3K27me3 identified genes that had specifically lost H3K27me3 upon EZH2 silencing. These findings suggested that stemness features are preserved via epigenetic mechanisms. Taken together, the genetic EWS-Fli1 translocation is intimately linked to global and gene specific epigenetic alterations in ET biology. EZH2 mediates neuroectodermal and endothelial embryonal tumor stem cell growth and metastasic spread induced by a translocation derived chimeric transcription factor. Keywords: PNET, Ewing Tumor Epigenetic regulation A673 transiently transfected with siRNA-EZH2 and siRNA-scrambled were harvested and Chromatin-IPs of H3K27me3 or H3 followed by microarray hybridisation were carried out. For detailed procedures see Burdach et al. Epigenetic Maintenance of Stemness and Malignancy in Peripheral Neuroectodermal Tumors by EZH2.

2010-05-18 | E-GEOD-15890 | biostudies-arrayexpress

Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth

Project description:Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth

| PRJNA796342 | ENA

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