Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The EZH2 and EZH1 inhibitor valemetostat derepresses p16INK4a to induce early endomitotic exit in megakaryocytes [RNA-Seq]

ABSTRACT: Polycomb repressive complex 2 (PRC2) represses transcription by trimethylation of histone H3 at lysine 27. Valemetostat is a potent inhibitor of enhancer of zeste homolog (EZH)2 and EZH1, which are histone methyltransferases of PRC2. PRC2 inhibitors, including valemetostat, have been showing promises in multiple cancer types. PRC2 inhibitors, however, can induce thrombocytopenia as a class adverse effect. To better understand valemetostat-induced thrombocytopenia, we performed single-cell ATAC-seq and bulk RNA-seq for human bone marrow CD34+ cells that were in vitro differentiated into megakaryocytes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270683 | GEO | 2026/06/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The EZH2 and EZH1 inhibitor valemetostat derepresses p16INK4a to induce early endomitotic exit in megakaryocytes [scATAC-Seq]

Project description:Polycomb repressive complex 2 (PRC2) represses transcription by trimethylation of histone H3 at lysine 27. Valemetostat is a potent inhibitor of enhancer of zeste homolog (EZH)2 and EZH1, which are histone methyltransferases of PRC2. PRC2 inhibitors, including valemetostat, have been showing promises in multiple cancer types. PRC2 inhibitors, however, can induce thrombocytopenia as a class adverse effect. To better understand valemetostat-induced thrombocytopenia, we performed single-cell ATAC-seq and bulk RNA-seq for human bone marrow CD34+ cells that were in vitro differentiated into megakaryocytes.

2026-06-25 | GSE270684 | GEO

Thyroid cancer-associated EZH1 Q571R mutation drives chromatin compaction and H3K27me3 invasion into active chromatin

Project description:Dysregulation of Polycomb Repressive Complex 2 (PRC2) contributes to cancer. Of its catalytic subunits, Enhancer of Zeste (EZH) 1 and EZH2, EZH2 mutations are extensively studied, but the role of EZH1 in cancer remains largely unexplored. Here, we investigate the thyroid cancer-associated EZH1 Q571R mutation and uncover a mechanism that extends beyond catalytic gain of function. Using biochemical, single-molecule, epigenomic, and transcriptomic analyses, we demonstrated that EZH1 Q571R significantly enhances chromatin compaction and stimulates PRC2-EZH1 catalytic activity, thereby rewiring PRC2 chromatin interactions. This altered engagement enables PRC2 activity within H3K36me2-marked chromatin typically refractory to H3K27 methylation, leading to widespread epigenetic and transcriptional reprogramming. Notably, enhanced chromatin compaction is observed with EZH1 Q571R but not with the corresponding EZH2 Q570R mutation, indicating an EZH1-specific mechanism. Functionally, EZH1 Q571R accelerated tumor growth in vivo and induced pronounced micronuclei formation ex vivo, reflecting aberrant chromatin compaction and genome instability. Together, our study demonstrates that EZH1 Q571R promotes a permissive epigenomic landscape for the progression of follicular thyroid cancer.

2026-07-03 | GSE294325 | GEO

Thyroid cancer-associated EZH1 Q571R mutation drives chromatin compaction and H3K27me3 invasion into active chromatin

2026-07-03 | GSE294323 | GEO

Thyroid cancer-associated EZH1 Q571R mutation drives chromatin compaction and H3K27me3 invasion into active chromatin

2026-07-03 | GSE294320 | GEO

Thyroid cancer-associated EZH1 Q571R mutation drives chromatin compaction and H3K27me3 invasion into active chromatin

2026-07-03 | GSE294321 | GEO

The quantitative analysis of transcriptomes derived from malignant rhabdoid tumor cells treated with EZH1/2 dual inhibitor or EZH2 selective inhibitor

Project description:We found that both EZH1 and EZH2 contributes to cell growth and H3K27 methylation, and EZH1/2 dual inhibitors induce growth inhibition in malignant rhabdoid tumor (MRT). To investigate the molecular mechanism underlying the growth inhibition of EZH inhibitors in MRT cells, we performed RNA-sequencing analysis and compared differentially expressed genes between A204.1 cells treated with EZH1/2 dual inhibitor DS-3201b or EZH2 selective inhibitor EPZ-6438.

2022-09-01 | GSE205086 | GEO

EZH1/2 inhibition improves immunotherapy response through MHC Class II de-repression and neutrophil reprogramming

Project description:Squamous cell carcinoma of the lung is a difficult-to-treat cancer with high prevalence in the US, and particularly in Kentucky. The goals of this work were to test if the EZH1/2 inhibitor valemetostat improves anti-PD1 responses in squamous cell lung cancer models, and to develop ex vivo models to test immunotherapy drug combinations. We found that valemetostat produced augmented anti-tumor responses to anti-PD1 therapy through up-regulation of tumor cell specific Major Histocompatibility Complex Class II (MHC Class II), and a shift towards activated CD8+ T cells . Neutrophils predominated in these tumors regardless of therapy, but examination of bone marrow revealed that valemetostat treated mice and mice that rejected tumors both had more mature neutrophils. Likewise, Ezh2 knock-out mice produced neutrophils that were more apoptotic, less migratory, and less able to produce extracellular nets, but had similar ability to kill bacteria as Ezh2-WT neutrophils. To test tumor responses to differing neutrophil populations, we engineered three-dimensional air-liquid interface cultures with tumoroids, lung mesenchymal cells, and T cells, with and without bone marrow containing neutrophils and myeloid progenitors from distinct donors. Bone marrow from tumor-naïve and mice with actively growing untreated tumors boosted tumoroid growth, while bone marrow from tumor-rejected and mice with tumors treated with valemetostat was anti-tumor. MHC Class II blockade lowered the ability of bone marrow to boost tumor growth and reduced the ability of valemetostat with anti-PD1 to reduce tumoroid growth. Patient samples revealed a strong negative correlation between EZH2 and MHC Class II, suggesting that targeting EZH2 activity could lead to marked increase in MHC Class II and improve treatment responses in lung squamous cell carcinomas.

2026-07-01 | GSE330733 | GEO

Relieving Dyrk1a repression of MKL1 corrects developmental defects in infantile megakaryocytes

Project description:Adult and fetal megakaryocytes are morphologically different. These differences contribute to neonatal thrombocytopenia in premature neonates and in neonates after infection and also contribute to poor megakaryocytes engrafment after umbilical cord blood transplant. We found that Dyrk1a kinase inhibition shift the fetal megakaryocytes phenotype toward adult phenotype. This effect is mediated by MKL1 the master regulator of megakaryocytes morphogenesis. To identify deferences between adult and fetal megakaryocytes we performed RNA seq of adult derived megakaryocytes and fetal derived megakaryocytes treated and untreated with Dyrk inhibitors. Through this approach we identified cohorts of genes co-regulated in adult megakaryocytes and fetal megakaryoctes treated with the dyrk inhibitors. More importantly, we found that the dyrk inhibition in fetal megakaryocytes leads to upregulation of a significant number of MKL1 target genes.

2022-08-30 | GSE195671 | GEO

Relieving Dyrk1a repression of MKL1 corrects developmental defects in infantile megakaryocytes

Project description:Adult and fetal megakaryocytes are morphologically different. These differences contribute to neonatal thrombocytopenia in premature neonates and in neonates after infection and also contribute to poor megakaryocytes engraftment after umbilical cord blood transplant. We found that Dyrk1a kinase inhibition shift the fetal megakaryocytes phenotype toward adult phenotype. This effect is mediated by MKL1 the master regulator of megakaryocytes morphogenesis. To identify differences between adult and fetal megakaryocytes we performed RNA seq of adult derived megakaryocytes and fetal derived megakaryocytes treated and untreated with Dyrk inhibitors. Through this approach we identified cohorts of genes co-regulated in adult megakaryocytes and fetal megakaryocytes treated with the dyrk inhibitors. More importantly, we found that the dyrk inhibition in fetal megakaryocytes leads to upregulation of a significant number of MKL1 target genes.

2022-05-29 | GSE204909 | GEO

Dual inhibition of EZH1/2 depletes stem cells and over-activates WNT signaling in multiple myeloma [ChIP-seq]

Project description:Multiple myeloma (MM) is a hematological malignancy caused by accumulation of abnormal clonal plasma cells. Despite the recent development of novel therapies, relapse of MM eventually occurs due to a remaining population of drug-resistant myeloma stem cells. Side population (SP) cells exhibit cancer stem cell-like characteristics in MM; thus targeting these cells is a promising strategy to completely cure this malignancy. Here, we showed that SP cells expressed higher levels of enhancer of zeste (EZH) 1 and EZH2, which encode the catalytic subunits of Polycomb repressive complex 2 (PRC2), than non-SP cells, suggesting that EZH1/2 are both potential therapeutic targets to eradicate myeloma stem cells. A novel EZH1/2 dual inhibitor, OR-S1, effectively eradicated SP cells and had a greater antitumor effect than a selective EZH2 inhibitor in vitro and in vivo, including in a patient-derived xenograft model. Moreover, long-term continuous administration of OR-S1 completely cured mice bearing orthotopic xenografts. Additionally, PRC2 directly regulated WNT signaling, and over-activation of this signaling induced by dual inhibition of EZH1/2 eradicated myeloma stem cells. Our results demonstrate that dual inhibition of EZH1/2 is a promising therapeutic approach to eradicate myeloma stem cells, leading to significant advances in the treatment of MM.

2019-01-25 | GSE109674 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data