Distinct roles of PARP-1 and PARP-2 in c-Myc-driven B cell Lymphoma in mice
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ABSTRACT:
PROVIDER: PRJNA602629 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10950319.fastq.gz | Fastqsanger.gz | |||
| SRR10950320.fastq.gz | Fastqsanger.gz | |||
| SRR10950321.fastq.gz | Fastqsanger.gz | |||
| SRR10950322.fastq.gz | Fastqsanger.gz | |||
| SRR10950323.fastq.gz | Fastqsanger.gz |
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Project description:To study the implication of PARP-1 deficiency or PARP-2 deficiency in the development of c-Myc overexpression-induced B lymphomas, we have studied by RNAseq the gene expression profile in pre-B cells isolated from bone marrow of mice that overexpress c-Myc in their B lymphocytes (WT) and in those mice with PARP-1 (KO1) or PARP-2 (KO2) deficiency
2021-12-31 | GSE144050 | GEO
Project description:Impact of CDK4-deficiency on EM-BM-5-myc driven B-lymphoma By crossing mating CDK4 Knockout mice with EM-BM-5-myc mice,We found CDK4-deficiency enhances the EM-BM-5-myc induced B-lymphoma.We further to discover the molecular mechanism B-lymphoma cells form the cdk4+/+ EM-BM-5-myc and cdk4-/-EM-BM-5-myc mice and then culturing for RNA extraction and hybridization on Affymetrix microarrays.
2012-12-16 | E-GEOD-21683 | biostudies-arrayexpress
Project description:Impact of CDK4-deficiency on Eµ-myc driven B-lymphoma By crossing mating CDK4 Knockout mice with Eµ-myc mice,We found CDK4-deficiency enhances the Eµ-myc induced B-lymphoma.We further to discover the molecular mechanism
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Project description:Myc is a well known transcription factor with important roles in cell cycle, apoptosis and cellular transformation. Long non-coding (lnc)RNAs have recently emerged as a important class of regulatory RNAs. Here, we show that lncRNAs are an extensive component of the Myc-regulated transcriptional program. Using the P493-6 inducible Myc model we demonstrate that both Myc-induced mRNAs and lncRNAs were significant enriched for Myc binding sites. In contrast to Myc-repressed mRNAs, Myc-repressed lncRNAs were significantly enriched for Myc binding sites. Subcellular localization analysis revealed that Myc-repressed lncRNAs and mRNAs are enriched in the nucleus while Myc-induced lncRNAs and mRNAs are enriched both in the cytoplasm and nucleus. Parallel analysis of differentially expressed lncRNAs and mRNAs identified 105 lncRNA-mRNA pairs that were in close vicinity, indicative for regulation in cis. To support the potential relevance of the Myc-regulated lncRNAs in cellular transformation, we analyzed their expression in primary Myc-high and Myc-low B-cell lymphomas. In total, 54% of the lncRNAs differentially expressed between the lymphoma subsets were identified as Myc-regulated in P493-6 cells. This study is the first to show that lncRNAs are an important factor within the Myc-regulated transcriptional program and indicates a marked difference between Myc-repressed lncRNAs and mRNAs. Expression of all known mRNAs and >10 000 lncRNAs was assessed in primary lymphoma tissue with high c-myc levels (Burkitt lymphoma; BL) and low c-myc levels (chronic lymphocytic leukemia; CLL)
2015-02-01 | E-GEOD-59479 | biostudies-arrayexpress
Project description:Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of BCR signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 (CBM) complex that transfers BCR signaling to the NF-kB pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls a MYC-driven gene expression network predominantly through increased MYC protein stability. Thus our analyses identify a previously unappreciated regulatory mechanism of MYC expression. Investigating primary mouse splenocytes, we could demonstrate that MALT1 induced MYC regulation is not restricted to MCL, but represents a common mechanism of MYC regulation. MYC itself is pivotal for MCL survival as its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL models. Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy in targeting the MALT1-MYC axis in MCL patients.
2017-02-24 | GSE81552 | GEO
Project description:MYC oncogenes are activated in broad spectrum of human malignancies and transcriptionally reprogram the genome to drive cancer cell growth. Given this it is unclear if targeting a single effector will have a therapeutic benefit. MYC activates the polyaminehypusine circuit, which post-translationally modifies the translation factor eIF5A. The hypusine axis has been proposed to suppress tumorigenesis. Here we report essential roles for hypusinated eIF5A in the development and maintenance of Myc-driven lymphoma, where loss of eIF5A hypusination abolishes malignant transformation. Mechanistically, integrating RNA-seq, Ribo-seq and proteomic analyses revealed that efficient translation of select targets is dependent upon eIF5A hypusination, including key regulators of G1 to S phase cell cycle progression. Notably, this circuit controls Myc’s proliferative response at several levels, and it is activated across multiple tumor types. These findings suggest the hypusine circuit as a therapeutic target for a broad spectrum of malignancies.
2024-01-26 | PXD031361 | Pride
Project description:To identify proteomic signatures associated with hepatocellular carcinoma driven by MYC overexpression, proteomics was performed on the LAP-tTA/tetO-MYC mouse conditional liver cancer model. Upon MYC activation, mice form liver cancer. Differential proteomics was performed in "MYC on" (MYC-HCC) mouse liver tumors versus mouse control normal liver tissue (where MYC was not overexpressed to drive tumorigenesis -- "MYC off").
2022-10-12 | PXD031478 | Pride
Project description:rDNA chromatin interactions in the MYC-driven Eµ-Myc transgenic mouse model of B-cell lymphoma
| PRJNA287914 | ENA
Project description:Background: MYC is a transcription factor encoded by the c-MYC gene (thereafter termed MYC). MYC is key transcription factor involved in many central cellular processes including ribosomal biogenesis. MYC is overexpressed in the majority of human tumours including aggressive B-cell lymphoma especially Burkitt's lymphoma. Although Burkitt's lymphoma is a highlight example for MYC overexpression due to a chromosomal translocation, no global analysis of MYC binding sites by chromatin immunoprecipitation (ChIP) followed by global next generation sequencing (ChIP-Seq) has been conducted so far in Burkitt's lymphoma. Methodology/Principal Findings: ChIP-Seq was performed with a MYC-specific antibody giving rise to 7,054 predicted MYC binding sites after bioinformatics analysis of a total of 19 million sequence reads. In line with previous findings, binding sites accumulate in gene sets known to be involved in the ribosomal biogenesis, histone acetyltransferase and methyltransferase complexes and the cell cycle demonstrating a regulatory role of MYC in these processes. Unexpectedly, MYC binding sites also accumulate in genes typically expressed in mature B-cells. To assess the functional consequences of altered MYC binding, the ChIP-Seq data were supplemented with siRNA mediated knock-downs of MYC in BL cell lines followed by gene expression profiling. Interestingly, amongst others, genes involved in B-cell function were up-regulated in response to MYC silencing. Conclusion/Significance: The 7,054 MYC-binding sites identified by our ChIP-Seq approach greatly extend the knowledge regarding MYC binding in Burkitt's lymphoma and sheds further light on the enormous complexity of the MYC regulatory network. Especially our observation that (i) many B-cell relevant genes are targeted by MYC and (ii) that MYC down-regulation leads to an up-regulation of B-cell genes highlights an interesting aspect of BurkittM-BM-4s lymphoma biology. [ChIP-Seq] Analysis of MYC DNA binding sites by ChiP-Seq in 5 BurkittM-BM-4s lymphoma cell lines (Raji, Ramos, Blue1, BL41, CA46) [mRNA expression profiling] siRNA-mediated knock-down of MYC was done employing the BL cell lines Raji, BL41 and Blue1 in order to detect MYC-driven gene expression changes. For this purpose, the cells were Amaxa-transfected using MYC smart pool siRNA and control siRNA (Thermo Scientific/Dharmacon, Erembodegem, Belgium), respectively.
2011-11-28 | E-GEOD-30726 | biostudies-arrayexpress
Project description:Many lymphoid malignancies arise from deregulated c-MYC expression in cooperation with additional genetic lesions. While many of these cooperative genetic lesions have been discovered and their functions characterised, DNA sequence data of primary patient samples suggest that many more do exist. However, the nature of their contributions to c-MYC driven lymphomagenesis have not yet been investigated. We identified TFAP4 as a potent suppressor of c-MYC driven lymphoma development in a previous genome-wide CRISPR knockout screen in primary cells in vivo. CRISPR deletion of TFAP4 in Eµ-MYC transgenic haematopoietic stem and progenitor cells (HSPCs) and transplantation of these manipulated HSPCs into lethally irradiated animals significantly accelerated c-MYC-driven lymphoma development. Interestingly, TFAP4 deficient Eµ-MYC lymphomas all arose at the pre-B cell stage of B cell development. This observation prompted us to characterise the transcriptional profile of pre-B cells from pre-leukaemic mice transplanted with Eµ-MYC/Cas9 HSPCs that had been transduced with sgRNAs targeting TFAP4. This analysis revealed that TFAP4 deletion reduced expression of several master regulators of B cell differentiation, such as Spi1, SpiB and Pax5, which are direct target genes of both TFAP4 and MYC. We therefore conclude that loss of TFAP4 leads to a block in differentiation during early B cell development, thereby accelerating c-MYC-driven lymphoma development.
2023-03-12 | GSE225684 | GEO