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Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T cell lymphoma [ChIP-seq]

ABSTRACT: Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T cell lymphoma [ChIP-seq]

PROVIDER: PRJNA813959 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18268861.fastq.gz	Fastqsanger.gz
	SRR18268862.fastq.gz	Fastqsanger.gz
	SRR18268863.fastq.gz	Fastqsanger.gz
	SRR18268864.fastq.gz	Fastqsanger.gz
	SRR18268865.fastq.gz	Fastqsanger.gz

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Similar Datasets

Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T cell lymphoma

Project description:Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T cell lymphoma

| PRJNA813838 | ENA

Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T cell lymphoma [RNA-seq]

Project description:Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T cell lymphoma [RNA-seq]

| PRJNA813960 | ENA

Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T cell lymphoma [ChIP-seq]

Project description:Peripheral T cell lymphoma (PTCL) is a heterogeneous group of hematological cancers arising from the malignant transformation of mature T cells. In a cohort of 28 PTCL cases, we identified recurrent overexpression of MYCN, a member of the MYC family of oncogenic transcription factors. Approximately half of all PTCL cases was characterized by a MYC expression signature. Inducible expression of MYCN in lymphoid cells in a mouse model caused T cell lymphoma that recapitulated human PTCL with a MYC expression signature. Integration of mouse and human expression data identified EZH2 as a key downstream target of MYCN. Remarkably, EZH2 was found to be an essential co-factor for the transcriptional activation of the MYCN-driven gene expression program, which was independent of methyltransferase activity, but dependent on phosphorylation by CDK1. MYCN-driven T cell lymphoma was sensitive to EZH2 degradation or CDK1 inhibition, which displayed synergy with FDA-approved HDAC inhibitors.

2022-09-01 | GSE198125 | GEO

Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T cell lymphoma [RNA-seq]

2022-09-01 | GSE198124 | GEO

Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T-cell lymphoma.

Project description:Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of hematological cancers arising from the malignant transformation of mature T cells. In a cohort of 28 PTCL cases, we identified recurrent overexpression of MYCN, a member of the MYC family of oncogenic transcription factors. Approximately half of all PTCL cases was characterized by a MYC expression signature. Inducible expression of MYCN in lymphoid cells in a mouse model caused T-cell lymphoma that recapitulated human PTCL with an MYC expression signature. Integration of mouse and human expression data identified EZH2 as a key downstream target of MYCN. Remarkably, EZH2 was found to be an essential cofactor for the transcriptional activation of the MYCN-driven gene expression program, which was independent of methyltransferase activity but dependent on phosphorylation by CDK1. MYCN-driven T-cell lymphoma was sensitive to EZH2 degradation or CDK1 inhibition, which displayed synergy with US Food and Drug Administration-approved histone deacetylase (HDAC) inhibitors.

| S-EPMC10653048 | biostudies-literature

Targeting EZH2 in MYCN-amplified Neuroblastoma [ChIP-seq]

Project description:Purpose: Identify new targets in MYCN-amplified Neuroblastoma Methods: ChIP-Seq experiments were performed on Kelly and LAN-1 neuroblastoma cells by using the following antibodies: anti-EZH2 (Cell Signaling 5246S); anti-H3K27me3 (Millipore 07-449); anti-H3K4me3 (Abcam ab8580). We evaluated the global EZH2 PRC2-dependence by identifiying direct genome-wide target genes for EZH2, H3K27me3 and H3K4me3. Results: We found that EZH2 serves a PRC2-dependent function in neuroblastoma, repressing neuronal differentiation. Moreover, EZH2-regulated genes were strongly repressed in MYCN-amplified and high-risk primary tumors. Conclusion: Our study supports testing EZH2 inhibitors in patients with MYCN-amplified neuroblastoma.

2017-12-02 | GSE85430 | GEO

Targeting EZH2 in MYCN-amplified Neuroblastoma [RNA-seq]

Project description:Purpose: Identify new targets in MYCN-amplified Neuroblastoma Methods: Kelly and LAN-1 neuroblastoma cells were treated in duplicate with 2 uM GSK126 (Excess Biosciences M60071-2) or DMSO for 2 or 5 days. RNA was extracted from cells with the RNeasy Kit (Qiagen). RNA libraries were prepared for sequencing using standard Illumina protocols. The pool of sixteen samples was sequenced on two lanes of an Illumina HiSeq, generating single end reads of 32-76 bp length. Transcript abundance (reads and FPKM scores) at GRCh37/hg19 RefSeq gene level was computed with the Feature Counts method implemented in the Bioconductor v3.2 Rsubread package (Liao et al., 2014). Results: Pharmacological suppression of EZH2 inhibited neuroblastoma growth. Transcriptomic analysis revealed that EZH2 serves a PRC2-dependent function in neuroblastoma, repressing neural differentiation. Moreover, EZH2-regulated genes were strongly repressed in MYCN-amplified and high risk primary tumors. These observations demonstrate that MYCN upregulates EZH2 leading to inactivation of a tumor suppressor program in neuroblastoma. Conclusion: Our study supports testing EZH2 inhibitors in patients with MYCN-amplified neuroblastoma.

2017-12-02 | GSE85431 | GEO

Targeting EZH2 in MYCN-amplified Neuroblastoma

Project description:Targeting EZH2 in MYCN-amplified Neuroblastoma

| PRJNA338446 | ENA

EZH2-dependent transcriptional complex promotes aberrant epithelial remodelling after injury

Project description:Unveiling the molecular mechanisms of tissue remodelling following injury is imperative to elucidate its regenerative capacity and aberrant repair in disease. Using different omics approaches, we identified enhancer of zester homolog 2 (EZH2) as a key regulator that initiates a fibrotic cascade in injured lung epithelium. Epithelial-injury-driven enrichment of nuclear transforming growth factor-b-activated kinase 1 (TAK1) mediates EZH2 phosphorylation to facilitate the release of EZH2 from polycomb repressive complex 2 (PRC2). This process leads to the establishment of a fibrotic transcriptional complex of EZH2, RNA-polymerase II (POL2) and nuclear actin, which orchestrates aberrant epithelial lung repair programs. The liberation of EZH2 from PRC2 is accompanied by an EZH2-EZH1 switch to preserve silencing at non-target genes. Loss of epithelial TAK1, EZH2 or blocking nuclear actin influx attenuates the fibrotic cascade and restores respiratory homeostasis. Accordingly, EZH2 inhibition significantly improves outcomes in a pulmonary fibrosis mouse model. Our results reveal an important non-canonical function of EZH2, paving the way for new therapeutic interventions in fibrotic lung diseases.

2021-04-27 | MSV000087321 | MassIVE

Targeting Histone Modification Crosstalk as a Therapeutic Strategy for EZH2-aberrant Solid Tumors

Project description:Mutations or aberrant upregulation of the histone methyltransferase EZH2 occur frequently in human cancers yet EZH2-targeted therapies have only shown very limited clinical benefits in hematological malignancies. We report here that upon EZH2 inhibition, MLL1 interacts with p300/CBP complex that directs H3K27me loss to gain of H3K27ac modification. This histone modification crosstalk leads to transcriptional reprogramming that restricts the therapeutic response to EZH2 inhibition. Concurrent inhibition of H3K27 methylation and acetylation results in transcriptional repression and growth dependency on the MAPK signaling pathway in a large cancer subset. In pre-clinical models encompassing a broad spectrum of EZH2-aberrant solid tumors, a combination of EZH2 and BRD4 inhibitors or a triple-combination including MAPK inhibition display robust efficacy with tolerable toxicity, in particular in liver and pancreatic cancers. Our results suggest an attractive precision treatment and patient stratification strategy for EZH2-aberrant tumors on the basis of intrinsic MLL1 expression and feedback MAPK activation.

2018-09-10 | PXD010842 |

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