PRMT2 links histone H3R8 asymmetric dimethylation to oncogenic activation and tumorigenesis of glioblastoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA433671 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6704110.fastq.gz | Fastqsanger.gz | |||
| SRR6704120.fastq.gz | Fastqsanger.gz | |||
| SRR6704111.fastq.gz | Fastqsanger.gz | |||
| SRR6704121.fastq.gz | Fastqsanger.gz | |||
| SRR6704112.fastq.gz | Fastqsanger.gz |
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Project description:Here we show that PRMT2 is highly expressed in GBM, which is correlated with poor prognosis. The silencing of PRMT2 inhibits GBM cell growth and glioblastoma stem cell self-renewal in vitro and suppreses orthotopic tumor growth. Transcriptome analysis demonstrated that PRMT2 depletion leads to significant deregulation of genes mainly associated with cell cycle progression and pathways in cancer. In agreement with previously published results, we show that PRMT2 is responsible for H3R8 asymmetric methylation (H3R8me2a) and that H3R8me2a enrichment at promoters and enhancers is closely correlated with known active histone marks. Furthermore, we show that PRMT2-mediated H3R8me2a is required for the maintenance of target gene expression and that the catalytic activity of PRMT2 is required for its protumorigenic functions. Taken together, this study demonstrates that PRMT2 acts as a transcriptional co-activator for oncogenic gene expression programs in GBM pathogenesis and provides a rationale for PRMT2 targeting in aggressive gliomas.
2018-08-22 | GSE110424 | GEO
Project description:Transcriptional deregulation has a vital role in glioblastoma multiforme (GBM). Thus, identification of epigenetic modifiers essential for oncogenic transcriptional programs is a key to designing effective therapeutics for this deadly disease. Here we report that Protein Arginine Methyltransferase 2 (PRMT2) is highly expressed in GBM and correlated with poor prognosis. The silencing or inactivation of PRMT2 inhibits GBM cell growth and glioblastoma stem cell self-renewal in vitro, and suppresses orthotopic tumor growth, accompanied with significant deregulation of genes mainly associated with cell cycle progression and pathways in cancer. Mechanistically PRMT2 is responsible for H3R8 asymmetric methylation (H3R8me2a), whose enrichment at promoters and enhancers is closely correlated with known active histone marks and is required for the maintenance of target gene expression. Together, this study demonstrates that PRMT2 acts as a transcriptional co-activator for oncogenic gene expression programs in GBM pathogenesis and provides a rationale for PRMT2 targeting in aggressive gliomas.
| S-EPMC6208368 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE29146: NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming [ChIP] GSE29147: NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming [RNAi] GSE29148: NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming [TKO] GSE29150: NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming [Transduction] Refer to individual Series
2011-11-29 | E-GEOD-29305 | biostudies-arrayexpress
Project description:Histone arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is crucial for transcription regulation and increasingly associated with cancer progression. However, some PRMTs present challenges as drug targets due to their unique, context-dependent activities. Here we report that hypoxia induces rapid condensation of PRMT2, which is required for its activity on histone H3R8 asymmetric dimethylation (H3R8me2a). Consistent with its roles in transcription activation, PRMT2 is enriched in transcriptional condensates and relies on its phosphorylation at Ser 12 (PRMT2S12ph). This phosphorylation, situated within the N-terminal intrinsic disordered regions of PRMT2, facilitates its integration into transcriptional condensates and H3R8me2a deposition. Consequently, PRMT2S12 phosphorylation is indispensable for transcription activation of the hypoxia-inducible genes and tumor progression in vivo. Notably, transcription-associated Cyclin-Dependent Kinases (CDK7-CDK9) is imperative for PRMT2S12 phosphorylation. As a result, CDK9 inhibitors suppress hypoxia-induced H3R8me2a activity and transcription, and they synergize with Temozolomide (TMZ) in halting tumor progression, partly reliant on blocking PRMT2S12ph. Therefore, our study uncovers novel roles of transcriptional condensation in augmenting methyltransferase activity and provide a fresh anti-cancer mechanism for CDK9 inhibitors by restricting context-dependent transcriptional programs.
2026-01-01 | GSE262581 | GEO
Project description:Histone arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is crucial for transcription regulation and increasingly associated with cancer progression. However, some PRMTs present challenges as drug targets due to their unique, context-dependent activities. Here we report that hypoxia induces rapid condensation of PRMT2, which is required for its activity on histone H3R8 asymmetric dimethylation (H3R8me2a). Consistent with its roles in transcription activation, PRMT2 is enriched in transcriptional condensates and relies on its phosphorylation at Ser 12 (PRMT2S12ph). This phosphorylation, situated within the N-terminal intrinsic disordered regions of PRMT2, facilitates its integration into transcriptional condensates and H3R8me2a deposition. Consequently, PRMT2S12 phosphorylation is indispensable for transcription activation of the hypoxia-inducible genes and tumor progression in vivo. Notably, transcription-associated Cyclin-Dependent Kinases (CDK7-CDK9) is imperative for PRMT2S12 phosphorylation. As a result, CDK9 inhibitors suppress hypoxia-induced H3R8me2a activity and transcription, and they synergize with Temozolomide (TMZ) in halting tumor progression, partly reliant on blocking PRMT2S12ph. Therefore, our study uncovers novel roles of transcriptional condensation in augmenting methyltransferase activity and provide a fresh anti-cancer mechanism for CDK9 inhibitors by restricting context-dependent transcriptional programs.
2026-01-01 | GSE262583 | GEO
Project description:Hypoxia-inducible transcription factors (HIFs) are crucial transcription factors for cellular response to low oxygen levels, but the key mediators for their downstream transcription activation are not well characterized. We previously found that PRMT2 activates target gene expression through its methyltransferase activity on histone H3R8. Here we find that PRMT2 expression is activated by HIF1 at hypoxic conditions. And PRMT2 activity is widely required for hypoxia-induced transcription activation. Accordingly, PRMT2 inactivation alleviates hypoxia-induced glioblastoma progression and chemotherapeutic resistance. And PRMT2 expression is associated with hypoxia signature
2024-04-01 | GSE235438 | GEO
Project description:Prmt1, an epigenetic regulatory gene, is the subject of our research aimed at identifying its interacting protein partners and elucidating the arginine sites within these proteins that undergo asymmetric dimethylation modification by Prmt1, utilizing the advanced technique of Liquid Chromatography-Tandem Mass Spectrometry (Lc-ms/ms).
2024-08-27 | PXD054515 | Pride
Project description:Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs) and is involved in various cellular processes, including cancer development. PRMT2 expression is increased in several cancer types although its role in acute myeloid leukemia (AML) remains unknown. Here, we investigate the role of PRMT2 in a cohort of patients with AML, PRMT2 knockout AML cell lines as well as a Prmt2 knockout mouse model. In patients, low PRMT2 expressors are enriched for inflammatory signatures, including the NF-κB pathway, and show inferior survival. In keeping with a role for PRMT2 in control of inflammatory signaling, bone marrow-derived macrophages from Prmt2 KO mice display increased pro-inflammatory cytokine signaling upon LPS treatment. In PRMT2-depleted AML cell lines, aberrant inflammatory signaling has been linked to overproduction of IL6, resulting from a deregulation of the NF-κB signaling pathway, therefore leading to hyperactivation of STAT3. Together, these findings identify PRMT2 as a key regulator of inflammation in AML.
2024-05-17 | GSE266252 | GEO
Project description:The goal of this study is to determine whether PRMT2 plays a causal role in the impairment of atherosclerosis regression in diabetes. We examined the consequence of deleting PRMT2 in myeloid cells during the regression of atherosclerosis in normal and diabetic mice. We found significant impairment of atherosclerosis regression under normoglycemic conditions in mice lacking PRMT2 (Prmt2-/-) in myeloid cells that mimic the decrease in regression of atherosclerosis in WT mice under diabetic conditions. This was associated with increased plaque macrophage retention. PRMT2-deficient plaque CD68+ cells under normoglycemic conditions showed increased expression of genes involved in cytokine signaling and inflammation compared to WT cells by RNA seq. Thus, the loss of PRMT2 is causally linked to impaired atherosclerosis regression.
2022-07-20 | GSE203523 | GEO
Project description:BRD4 functions as an epigenetic reader and plays a crucial role in regulating transcription and genome stability. Dysregulation of BRD4 is frequently observed in various human cancers. However, the molecular details of BRD4 regulation remain largely unknown. Here, we report that PRMT2- and PRMT4-mediated arginine methylation is pivotal for BRD4-dependent transcription, DNA repair, and tumor growth. Specifically, PRMT2/4 interact with and methylates BRD4 at R179, R181, and R183. This arginine methylation selectively controls a transcriptional program by promoting BRD4 enrichment at the hyper-acetylated chromatin regions. Moreover, BRD4 arginine methylation is induced by DNA damage and thereby promotes its binding to chromatin for DNA repair. Deficiency in BRD4 arginine methylation significantly suppresses tumor growth and sensitizes cells to BET inhibitors and DNA damaging agents. Therefore, our findings reveal an arginine methylation-dependent regulatory mechanism of BRD4 function and highlight targeting PRMT2/4 for better anti-tumor effect of BET inhibitors and DNA damaging agents.
2022-12-14 | GSE206667 | GEO