Hypoxia-inducible PRMT2 addiction in cancers
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA986065 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24980316.fastq.gz | Fastqsanger.gz | |||
| SRR24980317.fastq.gz | Fastqsanger.gz | |||
| SRR24980318.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 3 of 3 |
Similar Datasets
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: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:PRMT2 is implicated in adhesion-dependent cytoskeletal signaling and bone marrow engraftment in acute myeloid leukemia (AML). To define the transcriptional consequences of PRMT2 loss, we performed RNA sequencing of KG-1a AML cells comparing PRMT2 wild-type cells with independent CRISPR/Cas9-generated PRMT2 knockout clones. Differential expression analysis identified a common set of genes downregulated upon PRMT2 deletion. Gene ontology and gene set enrichment analyses showed that PRMT2 loss reduced transcriptional programs associated with leukocyte activation, cell adhesion, migration, and leukocyte cell-cell adhesion. These data support a role for PRMT2 in maintaining adhesion-associated transcriptional programs in AML cells and provide a transcriptomic resource linking PRMT2-dependent signaling to leukemic cell interaction with the bone marrow microenvironment.
2026-06-15 | GSE334988 | GEO
Project description:Oncogene-like addiction to aneuploidy in human cancers
| PRJNA921841 | ENA
Project description:Hypoxia-inducible factor 1a and Hypoxia in Tendon Fibroblasts
| PRJNA1456132 | ENA
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.
2023-03-11 | PXD034650 | Pride
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: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
Project description:We performed gene expression profiling of oligooxopiperazines (OPs) targeting the hypoxia-inducible transcription factor complex. Treatment of cells with OPs inhibited hypoxia-inducible gene expression in A549 cells.
2013-06-30 | GSE48134 | GEO