Prmt6 is an essential regulator of pluripotency and reprogramming
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE33635 | GEO | 2019/11/26
REPOSITORIES: GEO
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Project description:Zygotic genome activation (ZGA), which is according to the midblastula transition in zebrafish, is an important event during the maternal-zygotic transition in animals. Our preliminary study and other groupâs works indicate that epigenetic regulations play an essential role in ZGA. Morpholino was employed to knockdown PRMT6. We used microarrays to analyze the global gene expression in prmt6 morphants. prmt6 MO (0.3mM) was injected into the one-two cell zebrafish, prmt6 cMO (0.3mM) injection as a control. At 6 hpf, embryos were classified into three subtypes (normal, mild and severe) and prepared for global gene expression analysis with Affymetrix Zebrafish Genome Arrays. The severe subtype and the control were repeated three times.
2015-11-25 | E-GEOD-63735 | biostudies-arrayexpress
Project description:RNA-seq analysis was performed to identify key signaling responding to PRMT6 knockdown in MDA-MB-231
2023-05-24 | GSE210948 | GEO
Project description:Zygotic genome activation (ZGA), which is according to the midblastula transition in zebrafish, is an important event during the maternal-zygotic transition in animals. Our preliminary study and other group’s works indicate that epigenetic regulations play an essential role in ZGA. Morpholino was employed to knockdown PRMT6. We used microarrays to analyze the global gene expression in prmt6 morphants.
2015-11-25 | GSE63735 | GEO
Project description:To identify transcription factors of PRMT6 which could recruit PRMT6 to target genes, we used affinity purification of avi-tagged PRMT6 in combination with stable isotope labeling of amino acids in cell culture (SILAC) based mass spectrometry. For this, K562 cells were transduced with a lentiviral co expression vector for the BirA-ligase and avi-PRMT6 with a 21 amino acid taq, which is biotinylated in the cells. Cells expressing the BirA-ligase only served as a control. Avi-PRMT6 cells were grown in heavy SILAC medium and control cells in light SILAC medium for seven passages. Nuclear extracts were prepared from 1x108 cells and subjected to avi-PRMT6 affinity purification using magnetic streptavidin beads. Subsequently, the proteins were eluted from the beads. The eluates from the avi-PRMT6 and the control were mixed in a one to one ratio. Subsequently, we performed quantitative mass spectrometry (MS)-based analysis of the PRMT6 interactome.
2021-09-09 | PXD021804 | Pride
Project description:Purpose: Dysregulation of histone H3 arginine (R) methylation is still unknown in primary cancer including gastric cancer (GC), although PRMT6 plays a role in asymmetric dimethylation at H3R2 (H3R2me2as) in cancer cells. The objective is to clarify biological and molecular roles of H3R2me2as-PRMT6 pathway in GC. Experimental Design: We assessed H3R2me2as and PRMT6 levels in 133 primary GC tissues by immunohistochemistry. We analyzed biological functions of PRMT6 in GC cell lines using a lentivirus overexpression and CRISPR/Cas9-based knockout of PRMT6 systems. Results: Increased H3R2me2as was found in 68 GC (51.1%) cases and independently correlated with poor prognosis. PRMT6 was overexpressed in 70 (52.6%) GC, which strongly correlated with the H3R2me2as levels (P<0.001). PRMT6 overexpression in GC cells enhanced global H3R2me2as levels, cell invasiveness in vitro, while PRMT6-knockout GC cells suppressed these effects. PRMT6 knockout also impaired tumorigenicity in vivo. Microarray and ChIP assays demonstrated that PRMT6-knockout GC cells decreased the H3R2me2as levels at the promoter regions of PCDH7, SCD and IGFBP5, resulting in up-reregulation of their gene expression. PRMT6 recruited at the regions of PCDH7 and SCD in the PRMT6-overexpressed cells. Knockdown of tumor suppressor PCDH7 in PRMT6-knockout GC cells elevated cell migration and invasion. PRMT6 expression inversely correlated with PCDH7 expression in primary GC (P=0.021). Conclusions: H3R2me2as is a strong prognostic indicator of GC patients. Global and gene-specific H3R2me2as are maintained by PRMT6. PRMT6-overexpressed GC cells may acquire invasiveness through direct inhibition of PCDH7 by increasing H3R2me2as activity. Thus, PRMT6-H3R2me2as pathway is a promising new therapeutic target in GC.
2020-04-16 | GSE113188 | GEO
Project description:Purpose: Dysregulation of histone H3 arginine (R) methylation is still unknown in primary cancer including gastric cancer (GC), although PRMT6 plays a role in asymmetric dimethylation at H3R2 (H3R2me2as) in cancer cells. The objective is to clarify biological and molecular roles of H3R2me2as-PRMT6 pathway in GC. Experimental Design: We assessed H3R2me2as and PRMT6 levels in 133 primary GC tissues by immunohistochemistry. We analyzed biological functions of PRMT6 in GC cell lines using a lentivirus overexpression and CRISPR/Cas9-based knockout of PRMT6 systems. Results: Increased H3R2me2as was found in 68 GC (51.1%) cases and independently correlated with poor prognosis. PRMT6 was overexpressed in 70 (52.6%) GC, which strongly correlated with the H3R2me2as levels (P<0.001). PRMT6 overexpression in GC cells enhanced global H3R2me2as levels, cell invasiveness in vitro, while PRMT6-knockout GC cells suppressed these effects. PRMT6 knockout also impaired tumorigenicity in vivo. Microarray and ChIP assays demonstrated that PRMT6-knockout GC cells decreased the H3R2me2as levels at the promoter regions of PCDH7, SCD and IGFBP5, resulting in up-reregulation of their gene expression. PRMT6 recruited at the regions of PCDH7 and SCD in the PRMT6-overexpressed cells. Knockdown of tumor suppressor PCDH7 in PRMT6-knockout GC cells elevated cell migration and invasion. PRMT6 expression inversely correlated with PCDH7 expression in primary GC (P=0.021). Conclusions: H3R2me2as is a strong prognostic indicator of GC patients. Global and gene-specific H3R2me2as are maintained by PRMT6. PRMT6-overexpressed GC cells may acquire invasiveness through direct inhibition of PCDH7 by increasing H3R2me2as activity. Thus, PRMT6-H3R2me2as pathway is a promising new therapeutic target in GC.
2020-04-16 | GSE113189 | GEO
Project description:PRMT6, a type I arginine methyltransferase, di-methylates the arginine residues of both histones and non-histones asymmetrically. Increasing evidence indicates that PRMT6 plays a tumor mediator involved in human malignancies. Here, we aim to uncover the essential role and underlying mechanisms of PRMT6 in promoting glioblastoma (GBM) proliferation. Investigation of PRMT6 expression in glioma tissues demonstrated that PRMT6 is overexpressed, and elevated expression of PRMT6 is negatively correlated with poor prognosis in glioma/GBM patients. Silencing PRMT6 inhibited GBM cell proliferation and induced cell cycle arrest at the G0/G1 phase, while overexpressing PRMT6 had opposite results. Further, we found that PRMT6 attenuates the protein stability of CDKN1B by promoting its degradation. Subsequent mechanistic investigations showed that PRMT6 maintains the transcription of CDC20 by activating histone methylation mark (H3R2me2a), and CDC20 interacts with and destabilizes CDKN1B. Rescue experimental results confirmed that PRMT6 promotes the ubiquitinated degradation of CDKN1B and cell proliferation via CDC20. We also verified that the PRMT6 inhibitor (EPZ020411) could attenuate the proliferative effect of GBM cells. Our findings illustrate that PRMT6, an epigenetic mediator, promotes CDC20 transcription via H3R2me2a to mediate the degradation of CDKN1B to facilitate GBM progression. Targeting PRMT6-CDC20-CDKN1B axis might be a promising therapeutic strategy for GBM.
2023-03-31 | GSE221971 | GEO
Project description:Our data reveal that RNA m6A displays a sharp transition during leukemogenesis and involves in acquiring stem cell properties of leukemia stem cells (LSCs). We find that m6A reader IGF2BP2 and protein arginine methyltransferase PRMT6 play key roles in the acquisition of LSCs properties. Genetical deletion and pharmacological inhibition of PRMT6 delayed AML development. Mechanistically, IGF2BP2 regulates PRMT6 expression by stabilizing its mRNA in an m6A-dependent manner. PRMT6 further suppresses the expression of lipid transporter MFSD2A by establishing inactive H3R2me2a in its promoter region. Loss of PRMT6 and IGF2BP2 upregulates the expression of MFSD2A that increases the uptake of docosahexaenoic acid. Collectively, our findings uncover a critical role of IGF2BP2-PRMT6-MFSD2A signaling axis in AML development, and provide a promising therapeutic strategy for targeting LSCs.
2023-06-20 | GSE210279 | GEO
Project description:ES cells are able to self-renew and remain pluripotent. These characteristics are maintained by both genetic and epigenetic regulators. Protein arginine methyltransferase (PRMT) 4 and 5 are shown to be important in early embryonic development and in ES cells. PRMT6-mediated di-methylation of histone H3 at arginine 2 (H3R2me2) can antagonize the tri-methylation of histone H3 at lysine 4, which marks active genes. However, it is unclear whether PRMT6 and PRMT6-mediated H3R2me2 play crucial roles in early embryonic development and ES cell identity. In this study, we investigate their functions using mouse ES cells as the model. We used microarray (Affymetrix GeneChip Mouse Gene 1.0ST) to examine the global change of gene expression in mouse ES cells when Prmt6 was overexpressed and identified distinct classes of genes that are up-regulated and down-regulated during this process. Mouse ES cells were transfected with either pCAGIP.puro empty vector (control) or Prmt6 overexpressing plasmid (P+6 OE). After 3 days of selection by puromycin, cells from both populations were subjected to RNA extraction and hybridization on Affymetrix microarrays.
2011-03-04 | E-GEOD-27685 | biostudies-arrayexpress
Project description:Histone modification, a major epigenetic mechanism which regulates gene expression by chromatin remodeling, introduces dynamic changes in chromatin architecture. Protein arginine methyltransferase 6 (PRMT6) is overexpressed in various types of cancers. Epigenome regulates the expression of endogenous retrovirus (ERV), which activates interferon signaling related to cancer. We investigated the antitumor effects of PRMT6 inhibition and the role of PRMT6 in endometrial cancer (EC), using epigenome multi-omics analysis including assay for chromatin immunoprecipitation sequencing (ChIP-seq) and ribonucleic acid sequencing (RNA-seq). The expression of PRMT6 in EC was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). The prognostic impact of PRMT6 expression was evaluated using IHC. We investigated the effects of PRMT6-knockdown (KD) using cell viability and apoptosis assays, as well as its effects on the epigenome using ChIP-seq of H3K27ac antibodies and RNA-seq. Finally, we evaluated the downstream targets identified by multi-omics analysis. PRMT6 was overexpressed in EC and associated with a poor prognosis. PRMT6-KD induced histone hypomethylation, while suppressing cell growth and apoptosis. ChIP-seq revealed that PRMT6 regulated genomic regions related to interferons and apoptosis through histone modifications. RNA-seq data showed altered interferon-related pathways and increased expression of tumor suppressor genes, such as NKX6-1 and PIK3R1, after PRMT6-KD. RT-qPCR showed that eight ERV genes which activated interferon signaling were upregulated by PRMT6-KD. Our data suggested that PRMT6 inhibition induced apoptosis through interferon signaling activated by ERV. PRMT6 regulated tumor suppressor genes and may be a novel therapeutic target in EC.
2024-02-07 | GSE239294 | GEO