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Pol2 binding examined by ChIP-seq in inducible JMJD6 knockdown neuroblastoma cells

ABSTRACT: JMJD6 is an important oncogene that is upregulated in 17q21-ter gained neuroblastoma.It plays a role in E2F and N-Myc-regulated gene pathways and neuroblastoma tumorigenesis Using ChIP-Seq, We profiled RNA polymerase 2 binding in doxycycline inducible JMJD6 shRNA CHP-134 neuroblastoma cells, treated with either doxycycline or vehicle control. We identified a list of genes with reduced RNA Pol II binding peaks at their gene promoters as a result of the JMJD6 knockdown. GSEA analysis showed that the top four gene sets, with most considerable reduction in RNA Pol II binding peaks at gene promoters, were E2F target genes, G2M checkpoint genes, mitotic spindle genes, and Myc target genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE112919 | GEO | 2019/06/23

REPOSITORIES: GEO

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JMJD6 and NMYC binding examined by ChIP-seq in NMYC overexpressing CHP134 human neuroblastoma cells

Project description:JMJD6 (also known as PTDSR) is an important oncogene that is upregulated in 17q21-ter gained neuroblastoma.It plays a role in E2F and N-Myc-regulated gene pathways and neuroblastoma tumorigenesis Using ChIP-Seq, we profiled JMJD6 and NMYC binding in the NMYC overexpressing neuroblastoma cell line. We identified the genomic location of JMJD6 and NMYC binding peaks across the human genome.

2019-06-23 | GSE129588 | GEO

Metabolic reprogramming of cancer cells by JMJD6-mediated alternative splicing

Project description:Chromosome 17q gain occurs frequently in MYC-driven tumors including high-risk neuroblastoma. However, the biological consequences of this genetic event remain elusive. Here we show that JMJD6, frequently amplified at the chromosome 17q25 locus, is one of the essential genes to neuroblastoma cells that are engaged in pathways of mitochondrial metabolism, RNA processing and protein homeostasis. JMJD6 cooperates with MYC in cellular transformation and promotes cancer cell proliferation and tumor growth. Mechanistically, JMJD6 physically interacts with RNA-processing machinery to regulate the alternative splicing and protein synthesis. Notably, JMJD6 controls the alternative splicing of glutaminase (GLS), kidney-type glutaminase (KGA) and glutaminase C (GAC), a rate-limiting enzyme of glutaminolysis, and, consequently, the central carbon metabolism in neuroblastoma. Our findings indicate that JMJD6 coordinates with MYC in tumorigenesis by regulating cancer-promoting metabolic programs through an alternative pre-mRNA splicing mechanism.

2023-10-31 | GSE185867 | GEO

Metabolic reprogramming of cancer cells by JMJD6-mediated pre-mRNA splicing is associated with therapeutic response to splicing inhibitor

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2024-03-11 | GSE248283 | GEO

Differential gene expression analysis of MYCN-amplified neuroblastoma cells after Doxycycline inducible shRNA knockdown of JMJD6 gene expression

Project description:JMJD6 oncoprotein induces neuroblastoma and exerts its biological effects through modulation of downstream target genes. We identified that JMJD6 knockdown reduces neuroblastoma cell proliferation, so we investigated which downstream signaling pathways were regulated by JMJD6.

2019-06-23 | GSE112914 | GEO

H3K27ac, H3K4me and H3K4me3 binding examined by ChIP-seq in the CHP-134 neuroblastoma cell line

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CGH analysis of mouse mammary gland tumors from eight genetically-engineered mouse models

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Brd4 and JMJD6-associated Anti-pause Enhancers in Regulation of Transcriptional Pause Release

Project description:Distal enhancers characterized by H3K4me1 mark play critical roles in developmental and transcriptional programs. However, potential roles of specific distal regulatory elements in regulating RNA Polymerase II (Pol II) promoter-proximal pause release remain poorly investigated. Here we report that a unique cohort of jumonji C domain-containing protein 6 (JMJD6) and bromodomain-containing protein 4 (Brd4) co-bound distal enhancers, termed anti-pause enhancers (A-PEs), regulate promoter-proximal pause release of a large subset of transcription units via long-range interactions. Brd4-dependent JMJD6 recruitment on A-PEs mediates erasure of H4R3me2(s), which is directly read by 7SK snRNA, and decapping/demethylation of 7SK snRNA, ensuring the dismissal of the 7SKsnRNA/HEXIM inhibitory complex. The interactions of both JMJD6 and Brd4 with the P-TEFb complex permit its activation and pause release of regulated coding genes. The functions of JMJD6/ Brd4-associated dual histone and RNA demethylase activity on anti-pause enhancers have intriguing implications for these proteins in development, homeostasis and disease. All Gro-seq(s) were designed to reveal the transcriptional targets of JMJD6 and Brd4, and assess the role of JMJD6 and Brd4 in Pol II promoter-proximal pause release. All ChIP-seq(s) were designed to understand the unique features, associated molecular mechanisms and functions of the anti-pause enhancers (A-PEs) discovered in the current study.

2014-01-14 | E-GEOD-51633 | biostudies-arrayexpress

Pol2 binding examined by ChIP-seq in inducible JMJD6 knockdown neuroblastoma cells

Project description:Pol2 binding examined by ChIP-seq in inducible JMJD6 knockdown neuroblastoma cells

| PRJNA449504 | ENA

Dll4iDEC mouse liver endothelial cells

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2023-04-11 | PXD041349 | Pride

Mechanistic basis and efficacy of targeting Beta Catenin-TCF7L2-JMJD6-MYC Axis to overcome resistance to BET inhibitors [no drug]

Project description:Promising activity of BET protein inhibitors (BETis) is compromised by adaptive or innate resistance in AML. Here, modeling of BETi- persister/resistance (BETi-P/R) in human post-MPN secondary AML (sAML) cells demonstrated accessible and active chromatin in specific super-enhancers/enhancers, which was associated with increased levels of nuclear β-catenin, TCF7L2, JMJD6, and c-Myc in BETi-P/R sAML cells. Following BETi treatment, c-Myc levels were rapidly restored in BETi-P/R sAML cells. CRISPR/Cas9-mediated knockout of TCF7L2 or JMJD6 reversed BETi-P/R, whereas ectopic overexpression conferred BETi-P/R in sAML cells; confirming the mechanistic role of the β-catenin-TCF7L2- JMJD6-MYC axis in BETi-resistance. Patient-derived, post-MPN, CD34+ sAML blasts exhibiting relative resistance to BETi, as compared to sensitive sAML blasts, displayed higher mRNA and protein expressions of TCF7L2, JMJD6 and c-Myc, and following BETi washout exhibited rapid restoration of c-Myc and JMJD6. CRISPR/Cas9 knockout of TCF7L2 and JMJD6 depleted their levels, inducing loss of viability of the sAML blasts. Disruption of co-localization of nuclear β-catenin with TBL1 and TCF7L2 by the small molecule inhibitor BC2059 combined with depletion of BRD4 by BET-PROTAC reduced c-Myc levels and exerted synergistic lethality in BETi-P/R sAML cells. This combination also reduced leukemia burden and improved survival of mice engrafted with BETi-P/R sAML cells or with patient-derived AML blasts innately resistant to BETi. Therefore, multi- targeted disruption of β-catenin-TCF7L2-JMJD6-MYC axis overcomes adaptive and innate BETi-resistance, exhibiting pre-clinical efficacy against human post-MPN sAML cells.

2020-11-06 | GSE145275 | GEO

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