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Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma

ABSTRACT: Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma

PROVIDER: PRJNA656724 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12433440_1.fastq.gz	Fastqsanger.gz
	SRR12433440_2.fastq.gz	Fastqsanger.gz
	SRR12433441_1.fastq.gz	Fastqsanger.gz
	SRR12433441_2.fastq.gz	Fastqsanger.gz
	SRR12433442_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma [array]

Project description:Targeting PRMT5 in canine lymphoma: we characterized expression patterns of PRMT5 in canine lymphomas and correlated these with histological subtypes using tissue microarrays. We characterized expression of PRMT5 in three canine lymphoma-derived cell lines and primary lymph node biopsies. We have demonstrated that inhibition of PRMT5 leads to growth suppression and induction of apoptosis in canine lymphoma cell lines and primary canine lymphoma cells in a time and dose-dependent manner, while selectively decreasing global marks of symmetric dimethylarginine (SDMA) and histone H4 arginine 3 symmetric di-methylation. We performed ATAC-sequencing with pathway enrichment analysis to characterize genome-wide changes in chromatin accessibility after PRMT5 inhibition. We performed gene expression microarrays with pathway analysis to characterize whole transcriptome changes in canine lymphoma cell lines treated with PRMT5 inhibitors. This work validates PRMT5 as a promising therapeutic target for canine lymphoma and supports the continued used of the spontaneously occurring canine lymphoma model for the preclinical development of PRMT5 inhibitors for the treatment of human NHL.

2021-04-20 | GSE155599 | GEO

Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma [ATAC-seq]

2021-04-20 | GSE156084 | GEO

Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma [array]

Project description:Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma [array]

| PRJNA650415 | ENA

Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma [ATAC-seq]

Project description:Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma [ATAC-seq]

| PRJNA656732 | ENA

Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma.

Project description:Non-Hodgkin lymphoma (NHL) is a heterogeneous group of blood cancers arising in lymphoid tissues that commonly effects both humans and dogs. Protein arginine methyltransferase 5 (PRMT5), an enzyme that catalyzes the symmetric di-methylation of arginine residues, is frequently overexpressed and dysregulated in both human solid and hematologic malignancies. In human lymphoma, PRMT5 is a known driver of malignant transformation and oncogenesis, however, the expression and role of PRMT5 in canine lymphoma has not been explored. To explore canine lymphoma as a useful comparison to human lymphoma while validating PRMT5 as a rational therapeutic target in both, we characterized expression patterns of PRMT5 in canine lymphoma tissue microarrays, primary lymphoid biopsies, and canine lymphoma-derived cell lines. The inhibition of PRMT5 led to growth suppression and induction of apoptosis, while selectively decreasing global marks of symmetric dimethylarginine (SDMA) and histone H4 arginine 3 symmetric dimethylation. We performed ATAC-sequencing and gene expression microarrays with pathway enrichment analysis to characterize genome-wide changes in chromatin accessibility and whole-transcriptome changes in canine lymphoma cells lines upon PRMT5 inhibition. This work validates PRMT5 as a promising therapeutic target for canine lymphoma and supports the continued use of the spontaneously occurring canine lymphoma model for the preclinical development of PRMT5 inhibitors for the treatment of human NHL.

| S-EPMC8121334 | biostudies-literature

Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma

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

2021-04-20 | GSE156086 | GEO

Proteomics Profiling of Arginine Methylation Defines PRMT5 Substarate Specificity

Project description:Protein arginine methyltransferases (PRMTs) catalyze arginine methylation, an abundant post-translational modification occurring on both chromatin-bound and cytoplasmic proteins. Growing evidence supports the involvement of PRMT5, the major Type II PRMT, in pro-survival and differentiation pathways, important during development and to promote tumorigenesis. Thus, PRMT5 emerges as an attractive drug target and inhibitors are currently in clinical trials for cancer therapy. However, the knowledge of PRMT5 non-histone substrates is still limited, as are the dynamic changes in methylation levels upon its inhibition. Here, we employed a newly established pipeline coupling SILAC with methyl-peptides immuno-enrichment to globally profile arginine methylation following PRMT5 inhibition by GSK591 and adopted the heavy-methyl SILAC as orthogonal validation method to reduce false discovery rate. Then, in vitro methylation assays on a set of PRMT5 targets provided novel mechanistic insights into its strict preference to methylate arginine sandwiched between two neighbouring glycines (GRG). In conclusion, we identified novel PRMT5 substrates, thus providing the first proof of concept of the in vivo efficacy of PRMT5 inhibitor that impacts on arginine methylation beyond histones.

2019-04-10 | PXD009070 | Pride

PRMT5-mediated histone arginine methylation antagonizes transcriptional repression by polycomb complex PRC2 (ChIP-seq)

Project description:Protein arginine methyltransferase 5 (PRMT5) catalyzes the symmetric di-methylation of arginine residues in histones H3 and H4, marks generally associated with transcriptional repression. However, we found that PRMT5 inhibition (or depletion) led to more genes being down-regulated than up-regulated, indicating that PRMT5 can also act as a transcriptional activator. Indeed, the global level of histone H3K27me3 increases in PRMT5 deficient cells. Although PRMT5 does not directly affect PRC2 enzymatic activity, methylation of histone H3 by PRMT5 abrogates its subsequent methylation by PRC2. Treating AML cells with an EZH2 inhibitor partially restored the expression of approximately 50% of the genes that are initially down-regulated by PRMT5 inhibition, suggesting that the increased H3K27me3 contributes to the transcription repression of these genes. Interestingly, the growth inhibitory effect of PRMT5 inhibition was also partially rescued by combined treatment with EZH2 inhibitor in several leukemia cell lines. Thus, PRMT5-mediated crosstalk between histone marks contributes to its functional effects.

2021-05-30 | GSE142764 | GEO

PRMT5-mediated histone arginine methylation antagonizes transcriptional repression by polycomb complex PRC2 (RNA-seq)

2021-05-30 | GSE132407 | GEO

PRMT5-mediated histone H4 arginine-3 symmetrical dimethylation marks chromatin at G+C-rich regions of the mouse genome.

Project description:Symmetrical dimethylation on arginine-3 of histone H4 (H4R3me2s) has been reported to occur at several repressed genes, but its specific regulation and genomic distribution remained unclear. Here, we show that the type-II protein arginine methyltransferase PRMT5 controls H4R3me2s in mouse embryonic fibroblasts (MEFs). In these differentiated cells, we find that the genome-wide pattern of H4R3me2s is highly similar to that in embryonic stem cells. In both the cell types, H4R3me2s peaks are detected predominantly at G + C-rich regions. Promoters are consistently marked by H4R3me2s, independently of transcriptional activity. Remarkably, H4R3me2s is mono-allelic at imprinting control regions (ICRs), at which it marks the same parental allele as H3K9me3, H4K20me3 and DNA methylation. These repressive chromatin modifications are regulated independently, however, since PRMT5-depletion in MEFs resulted in loss of H4R3me2s, without affecting H3K9me3, H4K20me3 or DNA methylation. Conversely, depletion of ESET (KMT1E) or SUV420H1/H2 (KMT5B/C) affected H3K9me3 and H4K20me3, respectively, without altering H4R3me2s at ICRs. Combined, our data indicate that PRMT5-mediated H4R3me2s uniquely marks the mammalian genome, mostly at G + C-rich regions, and independently from transcriptional activity or chromatin repression. Furthermore, comparative bioinformatics analyses suggest a putative role of PRMT5-mediated H4R3me2s in chromatin configuration in the nucleus. High throughput sequencing data from H4R3me2s native ChIP samples from mouse embryonic stem cells and fibroblasts were generated using Illumina Hi-seq 2000.

2013-10-04 | E-GEOD-37604 | biostudies-arrayexpress

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