Expression data from mouse pancreatic cell lines treated with chromatin-targeting small molecules
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE36379 | GEO | 2012/03/09
SECONDARY ACCESSION(S): PRJNA153261
REPOSITORIES: GEO
Similar Datasets
Project description:We measured the genome-wide expression changes induced by 29 compounds targeting HDACs, DNMTs, histone lysine methyltransferases (HKMTs), and protein arginine methyltransferases (PRMTs) in pancreatic M-NM-1- and M-NM-2-cell lines. We used microarrays to detail the global programme of gene-expression changes induced by chromatin-targeting compounds at 1, 6, and 24 hours. To identify a comprehensive list of target genes that can be regulated by modulating the activities of chromatin-modifying enzymes, we measured the genome-wide transcriptional effects of 29 compounds in pancreatic alpha and beta cell lines at three time points. The results indicate that compounds cause similar effects independent of the cell line in which they were profiled. All clinical HDAC inhibitors fell into the structural classes of hydroxamic acids and ortho-amino anilides, respectively and up- and down-regulated hundreds of transcripts. In contrast, more selective compounds like the HKMT inhibitor BIX-01294 have specific effects.
2012-03-09 | E-GEOD-36379 | biostudies-arrayexpress
Project description:In filamentous fungi, arginine methylation has been implicated in morphogenesis, mycotoxin biosynthesis, pathogenicity, and stress response although the exact role of this posttranslational modification in these processes remains obscure. Here, we present the first genome-wide transcriptome analysis in filamentous fungi that compared expression levels of genes regulated by type I and type II protein arginine methyltransferases (PRMTs).
2019-06-01 | GSE132039 | GEO
Project description:Histone arginine methylation, which is catalyzed by protein arginine methyltransferases (PRMTs), plays a key regulatory role in various biological processes, including signal transduction, RNA splicing, transcription and chromatin remodeling, and DNA repair. Several PRMTs are involved in skeletal development; however, their role in the osteogenic differentiation of mesenchymal stem cells (MSCs) is not completely clear. In this study, we aimed to elucidate the function of PRMT3, a type-I PRMT that catalyzes the formation of ω-mono- or asymmetric dimethyl arginine, in MSC osteogenesis. We found that PRMT3 is involved in MSC osteogenic commitment and bone remodeling. Then we did PRMT3 and H4R3me2a ChIP-seq in MSC to find the possible target genes.
2019-08-20 | GSE124674 | GEO
Project description:Type I Protein Arginine Methyltransferases (PRMTs) catalyze asymmetric dimethylation of arginine residues on numerous proteins. Type I PRMTs and their substrates have been implicated in human cancers, suggesting that inhibiting Type I PRMT activity offers a tractable approach for therapeutic intervention. This dataset contains results from immunoproteomic studies enriching for monomethylated, asymmetrically, and symmetrically dimethylated arginines in cancer cell lines treated with the Type I PRMT inhibitor, GSK3368712.
2019-09-10 | PXD012747 | Pride
Project description:Under inflammatory conditions the extravasation of monocytes into tissues through trans-endothelial migration is a fundamental immunological process underlying innate inflammatory responses across multiple organ systems contributing to tissue injury and the progression of autoimmunity, cardiovascular disease and particularly chronic lung disease. Methylation of protein arginine residues via protein arginine methyltransferases (PRMTs) is a post-translational epigenetic modification implicated in inflammatory responses. How PRMTs, particularly PRMT7, epigenetically regulates monocyte-driven inflammatory response in disease remains unclear. Here, we perform ATAC-seq analysis on an MHS macrophage cell line in which PRMT7 has been disrupted by CRISPR/Cas9 to examine chromatin accessibility regulated by PRMT7.
2022-01-12 | GSE153666 | GEO
Project description:Paclitaxel -resistant triple negative breast cancer (TNBC) remains one of the most challenging breast cancers to treat. Using an epigenetic chemical probe screen, we uncover an acquired vulnerability of paclitaxel-resistant TNBC cells to protein arginine methyltransferases (PRMTs) inhibition. Analysis of cell lines and in-house clinical samples demonstrates that resistant cells evade paclitaxel killing through stabilizing mitotic chromatin assembly. Genetic or pharmacologic inhibition of PRMT5 alters RNA splicing, particularly intron retention of Aurora kinases B (AURKB), leading to a decrease in protein expression, and finally results in selective mitosis catastrophe in paclitaxel-resistant cells. These findings are fully recapitulated in a patient derived xenograft (PDX) model generated from a paclitaxel-resistant TNBC patient, providing the rationale for targeting PRMTs in paclitaxel-resistant TNBC.
2024-06-21 | GSE264630 | GEO
Project description:The enzymatic activities of protein methyltransferases serve to write covalent modifications on histone and non-histone proteins in the control of gene transcription. Here, we describe gene expression changes in human endothelial cells caused by treatment with methyltransferase inhibitors 7,7'-carbonylbis (azanediyl) bis(4-hydroxynaphthalene-2 -sulfonic acid (AMI-1) and disodium-2-(2,4,5,7- tetrabromo-3-oxido-6-oxoxanthen-9-yl) benzoate trihydrate (AMI-5). Deep sequencing of mRNA indicated robust change on transcription following AMI-5 treatment compared with AMI-1. Functional annotation analysis revealed that both compounds suppress the expression of genes associated with translational regulation, suggesting arginine methylation by protein arginine methyltransferases (PRMTs) could be associated with regulation of this pathway. Interestingly, AMI-5 but not AMI-1 was found to decrease methylation of H3 histones at lysine 4 and down-regulate gene expression associated with interleukin-6 (IL-6) and activator protein-1 (AP-1) signaling pathways. These results imply that inhibition of protein methylation by AMI-1 and AMI-5 can differentially regulate specific pathways with potential to interrupt pathological signaling in the vascular endothelium.
2017-01-07 | GSE93237 | GEO
Project description:Aberrant protein arginine methylation has been observed in multiple cancer types, making it an attractive drug target. Proteins can undergo asymmetric arginine methylation by type I protein arginine methyltransferases (PRMTs), predominately by PRMT1 and to a lesser extent PRMT4, or symmetric arginine methylation by type II PRMTs, predominately PRMT5. Here, we performed targeted proteomics following inhibition of PRMT1, PRMT4, and PRMT5 across cancer cell lines. We found that inhibition of both type I and type II PRMTs suppressed levels of total and phosphorylated ATR protein in cancer cell lines, and down-regulated expression of the ATR gene. Loss of ATR from PRMT inhibition resulted in defective DNA replication stress response activation in following exogenous replication stress. Since PARP inhibitors are known to induce replication stress, we next combined PRMT inhibition with PARP inhibition and found inhibition of PRMT1 or PRMT5 greatly exacerbated PARP inhibitor induced DNA damage. Based on this observation, we assessed the combination of PARP and PRMT inhibition in a panel of cell lines. While inhibition of both type I and type II PRMTs were synergistic with PARP inhibition in both cells with intact and deficient homologous recombination, type I PRMT inhibition resulted in higher toxicity in non-malignant cells. Therefore, we validated the synergy of combined PARP/PRMT5 inhibition in primary patient-derived organoids. Finally, we demonstrate that the combination of PARP and PRMT5 inhibition improves overall survival in both BRCA-mutant and wild-type patient-derived xenograft models without any detectable hematological toxicities typically associated with PARPi combination therapies. Taken together, these results demonstrate that PRMT5 inhibition may be a well-tolerated approach to improve tumor sensitivity to PARP inhibition. .
2023-10-26 | GSE246325 | GEO
Project description:Genes repressed by DNA methylation can be derepressed by various compounds targeting DNA methyltransferases, histone deacetylases, etc. Here, we report a high throughput screen against a 308,251-member chemical library aiming to identify novel small molecules that derepress an EGFP reporter gene silenced by DNA methylation. RNA-seq was used to measure mRNA abundance in control and compound-treated cells.
2018-03-12 | GSE106573 | GEO
Project description:Protein arginine methyltransferases (PRMTs) are required for the regulation of RNA processing factors. Type I PRMT enzymes catalyze mono- and asymmetric dimethylation; Type II enzymes catalyze mono- and symmetric dimethylation. To understand the specific mechanisms of PRMT activity in splicing regulation, we inhibited Type I and II PRMTs and probed their transcriptomic consequences. Using the newly developed Splicing Kinetics and Transcript Elongation Rates by Sequencing (SKaTER-seq) method, analysis of co-transcriptional splicing demonstrated that PRMT inhibition resulted in altered splicing rates. Surprisingly, co-transcriptional splicing kinetics did not correlate with final changes in splicing of polyadenylated RNA. This was particularly true for retained introns (RI). By using actinomycin D to inhibit ongoing transcription, we determined that PRMTs post-transcriptionally regulate RI. Subsequent proteomic analysis of both PRMT-inhibited chromatin and chromatin-associated polyadenylated RNA identified altered binding of many proteins, including the Type I substrate, CHTOP, and the Type II substrate, SmB. Targeted mutagenesis of all methylarginine sites in SmD3, SmB, and SmD1 recapitulated splicing changes seen with Type II PRMT inhibition, without disrupting snRNP assembly. Similarly, mutagenesis of all methylarginine sites in CHTOP recapitulated the splicing changes seen with Type I PRMT inhibition. Examination of subcellular fractions further revealed that RI were enriched in the nucleoplasm and chromatin. Together, these data demonstrate that, through Sm and CHTOP arginine methylation, PRMTs regulate the post-transcriptional processing of nuclear, detained introns.
2022-01-08 | GSE163421 | GEO