| 2001 |
PRMT6 is a nuclear type I protein arginine methyltransferase that catalyzes both omega-N(G)-monomethylarginine and asymmetric omega-N(G),N(G)-dimethylarginine on glycine- and arginine-rich substrates in a processive manner, and is the first PRMT to display automethylation activity. It resides solely in the nucleus when fused to GFP and has distinct substrate specificity compared to PRMT1 and PRMT4. |
GST fusion protein in vitro methylation assay, GFP fusion subcellular localization, substrate specificity comparison |
The Journal of biological chemistry |
High |
11724789
|
| 2007 |
PRMT6 methylates histone H3 at R2 (H3R2me2a) in vitro and in vivo and is the major H3R2 methyltransferase in cells. H3R2 methylation by PRMT6 inhibits H3K4 trimethylation by blocking WDR5 (a subunit of the MLL complex) binding to H3 in vitro, thereby repressing transcription of Hox and Myc-dependent genes. Upon retinoic acid-induced transcriptional activation, PRMT6 recruitment and H3R2me2a decrease while H3K4me3 increases. |
In vitro histone methylation assay, overexpression/knockdown analysis, ChIP, reporter assays, cell differentiation model |
Genes & development |
High |
18079182
|
| 2007 |
PRMT6 methylates HIV-1 Tat at R52 and R53, reducing Tat binding to TAR RNA and impairing Tat-TAR-cyclin T1 ternary complex formation, thereby reducing cyclin T1-dependent Tat transcriptional activation. A methylase-inactive PRMT6 mutant did not reduce Tat transactivation. PRMT6 knockdown increased HIV-1 production. |
In vitro and in vivo methylation assay, site-directed mutagenesis, luciferase/CAT reporter assays, siRNA knockdown, cell-based HIV replication assay |
Journal of virology |
High |
17267505
|
| 2006 |
PRMT6 methylates HIV-1 Rev at a single arginine in its N-terminal arginine-rich motif, reducing Rev binding to the RRE and Rev-mediated viral RNA export from nucleus to cytoplasm. Wild-type but not methylase-inactive PRMT6 reduced Rev-RRE binding and export. PRMT6 also reduces Rev protein levels through a post-translational mechanism independent of methyltransferase activity. |
In vitro methylation assay, co-immunoprecipitation, CAT reporter RNA export assay, site-directed mutagenesis of Rev arginines |
Retrovirology |
High |
17176473
|
| 2009 |
PRMT6 directly represses the thrombospondin-1 (TSP-1) promoter by associating with it and maintaining H3R2me2a while suppressing H3K4me3. In PRMT6-deficient cells H3R2 is hypomethylated and H3K4 trimethylated at the TSP-1 promoter, leading to TSP-1 upregulation and cell migration defects that are rescued by blocking secreted TSP-1. |
ChIP, microarray, siRNA knockdown, TSP-1 promoter reporter assay, cell migration assay, neutralizing antibody rescue |
The Journal of biological chemistry |
High |
19509293
|
| 2011 |
PRMT6 catalyzes H2AR29 asymmetric dimethylation (H2AR29me2), a novel repressive histone mark enriched at PRMT6-repressed genes. PRMT1 and PRMT6 are unique among PRMTs in methylating H2A at R11 and R29. |
Biochemical methylation assay with candidate enzymes, mass spectrometry identification of methylation sites, ChIP at repressed genes |
Epigenetics & chromatin |
High |
21774791
|
| 2012 |
PRMT6 knockout MEFs undergo premature senescence via p53-dependent induction of p53, p21, and PML. ChIP revealed PRMT6 and H3R2me2a enrichment at the Trp53 upstream region; in PRMT6-/- MEFs this mark is lost, H3K4me3 increases, and p53 transcription rises. Double KO with p53 prevents senescence, placing PRMT6 upstream of p53. |
PRMT6-/- MEF generation, ChIP, genetic epistasis (PRMT6-/-;p53-/- double KO), growth assays |
Nucleic acids research |
High |
22904064
|
| 2012 |
PRMT6 directly represses the p21 (CDKN1A) promoter via H3R2me2a in a p53-independent manner. PRMT6 knockdown in breast cancer cells causes p21 derepression, G1 arrest, and cellular senescence; bypassing p21-mediated arrest rescues these phenotypes. |
siRNA knockdown, promoter ChIP, cell cycle analysis, senescence assays, soft agar and xenograft assays, rescue by p21 bypass |
Nucleic acids research |
High |
22987071
|
| 2012 |
PRMT6 represses p21 and p27 gene expression through H3R2me2a deposited at their promoters, regulating cell cycle progression; knockdown of PRMT6 causes G2 arrest in U2OS cells with upregulation of p21 and p27. In oncogene-induced senescence, PRMT6 expression declines and p21 rises; PRMT6 overexpression reduces OIS. |
siRNA knockdown, ChIP, cell cycle analysis, OIS cell model, promoter analysis |
PloS one |
High |
22916108
|
| 2012 |
PRMT6 methylates the tumor suppressor p16 (INK4A) at R22, R131, and R138, reducing p16-CDK4 association and counteracting G1 cell cycle arrest induced by p16. |
In vitro methylation assay, site-directed mutagenesis, co-immunoprecipitation, flow cytometry, Western blot |
The international journal of biochemistry & cell biology |
Medium |
23032699
|
| 2012 |
PRMT6 uses a rapid equilibrium random kinetic mechanism (not ordered) with dead-end EAP and EBQ complexes, as determined with the AcH4-21 and R1 peptides and their monomethylated versions. |
Initial velocity, product inhibition, and dead-end analog inhibition kinetic studies |
The Journal of biological chemistry |
High |
22219200
|
| 2013 |
PRMT6 automethylates at R35 (identified by LC-MS and confirmed by mutagenesis). Automethylation at R35 is required for PRMT6 protein stability and its anti-HIV-1 activity in single-cycle infectivity assays. |
LC-MS, site-directed mutagenesis, in vitro and in vivo methylation assays, HIV-1 TZM-bl infectivity assay |
Retrovirology |
High |
23866860
|
| 2013 |
PELP1 interacts with PRMT6 and co-regulates alternative splicing and estrogen receptor target gene expression; PRMT6 inhibition reduces PELP1-mediated ER activation, proliferation, and colony formation. PELP1 and PRMT6 co-occupy ER target gene promoters affecting H3R2me2a. |
Co-immunoprecipitation, RNA-seq, ChIP, reporter assays, siRNA knockdown, proliferation/colony assays |
Molecular oncology |
Medium |
24447537
|
| 2013 |
PRMT6 methylates GPS2, facilitating its interaction with TBL1 and protecting GPS2 from Siah2-mediated polyubiquitination and proteasomal degradation, thereby regulating GPS2 nuclear function. |
Co-immunoprecipitation, ubiquitination assay, methylation assay, protein stability assay |
The Journal of biological chemistry |
Medium |
26070566
|
| 2013 |
PRMT6 differentially regulates MHC class II isotype expression: through an AT-hook motif of RFX5, PRMT6 downregulates HLA-DQ but not HLA-DR transcription in an AT-hook-dependent manner. |
Promoter reporter assay, methylation analysis, mutant RFX5 constructs, gene expression analysis |
Molecular immunology |
Medium |
23911394
|
| 2013 |
Yeast two-hybrid screen and in vitro methylation assays identified 36 putative PRMT6 partners; 7 were validated by co-IP in vivo; 4 new substrates were confirmed including HMGA1a. HMGA1a modulates PRMT6 methyltransferase activity. |
Yeast two-hybrid, co-immunoprecipitation, in vitro methylation assay |
PloS one |
Medium |
23326497
|
| 2014 |
PRMT6 functions as a NF-κB coactivator: it directly interacts with RelA, is recruited by RelA to selective NF-κB target promoters upon TNF-α stimulation, enhances NF-κB reporter transcriptional activity, and causes RelA nuclear accumulation. In a tamoxifen-inducible transgenic mouse model, ER*-PRMT6 activation increases IL-6 levels. |
Transgenic mouse gain-of-function model, co-immunoprecipitation, ChIP, NF-κB reporter assay, cytokine measurement |
Nucleic acids research |
High |
24939901
|
| 2015 |
PRMT6 methylates p21 (CDKN1A) at R156 and promotes phosphorylation of T145, resulting in increased cytoplasmic localization of p21 and resistance to cytotoxic agents. |
In vitro methylation assay, site-directed mutagenesis, subcellular fractionation, cell viability assay |
Oncotarget |
Medium |
26436589
|
| 2015 |
PRMT6 inhibits HIV-1 Tat nucleolar retention in a methylation-dependent manner: overexpression of catalytically active (but not inactive) PRMT6 excludes Tat from the nucleolus; R52/53A Tat mutant does not show redistribution. FRAP analysis indicates Tat nucleolar accumulation is through binding to nucleolar components, blocked by PRMT6 methylation at R52/53. |
Fluorescence microscopy, FRAP, site-directed mutagenesis, catalytically inactive mutant control |
Biochimica et biophysica acta |
Medium |
26611710
|
| 2015 |
EPZ020411 was identified as the first potent, selective small-molecule PRMT6 inhibitor tool compound with good bioavailability following subcutaneous dosing in rats. |
Biochemical inhibitor assay, selectivity profiling, pharmacokinetic measurement in rats |
ACS medicinal chemistry letters |
Medium |
26101569
|
| 2015 |
PRMT6 is required for zebrafish early development (epiboly); it directly represses gadd45αa via H3R2me2a, and loss of PRMT6 activates p38/JNK pathway and apoptosis. gadd45αa morpholino and p38/JNK inhibitors partially rescue prmt6 morphant defects. |
Morpholino knockdown in zebrafish, mRNA rescue, microarray, ChIP-qPCR, luciferase reporter, pharmacological inhibitors |
The Journal of biological chemistry |
High |
26487724
|
| 2016 |
Crystal structures of human PRMT6 in complex with SAH, a bisubstrate inhibitor (GMS), and an arginine-containing peptide were solved. Structural analysis reveals the determinants of asymmetric vs. symmetric dimethylarginine product specificity among PRMT types. |
X-ray crystallography, bisubstrate inhibitor synthesis, in vitro methylation inhibition assay |
The Biochemical journal |
High |
27480107
|
| 2017 |
PRMT6 overexpression impairs chromatin association of UHRF1 (an accessory factor of DNMT1), likely via elevated H3R2me2a inhibiting UHRF1-H3 interaction, resulting in passive DNA demethylation and global DNA hypomethylation in cancer. |
Overexpression/knockdown studies, bisulfite sequencing for DNA methylation, chromatin fractionation, co-IP, UHRF1-H3 interaction assay |
Cell reports |
Medium |
29262320
|
| 2018 |
PRMT6 methylates CRAF at arginine 100 (R100), decreasing CRAF's RAS binding potential and altering downstream MEK/ERK signaling; loss of PRMT6 promotes hepatocellular carcinoma stem cell properties. |
Co-immunoprecipitation, in vitro methylation assay, mass spectrometry, PRMT6 KO mouse model, organoid culture, transcriptome/protein-protein interaction analysis |
Cell reports |
High |
30332648
|
| 2018 |
PRMT6 inhibits antiviral innate immunity by binding IRF3 and blocking TBK1-IRF3 interaction, thereby inhibiting IRF3 activation and type-I interferon production. This function is independent of PRMT6 methyltransferase activity. PRMT6-deficient mice show enhanced antiviral immunity. |
PRMT6-/- mouse generation, co-immunoprecipitation, IFN-β reporter assay, viral infection assays, methyltransferase-inactive mutant |
Cellular & molecular immunology |
High |
29973649
|
| 2018 |
PRMT6 is recruited to H3R2me2a-marked promoters and enhancers during neural differentiation; loss of H3R2me2a at promoters leads to enhanced KMT2A binding and H3K4me3, increasing transcription, while loss at enhancers leads to reduced KMT2D binding and H3K4me1/H3K27ac, decreasing transcription—indicating context-dependent dual transcriptional roles. |
PRMT6 KO cell model, ChIP-seq, H3R2me2a genome-wide mapping, differentiation assays |
Cell reports |
High |
30232013
|
| 2019 |
PRMT6 physically associates with PTEN and asymmetrically dimethylates it at R159, suppressing PI3K-AKT signaling. PTEN R159K mutant found in cancers loses its ability to inhibit PI3K-AKT. PRMT6-mediated PTEN methylation also modulates pre-mRNA alternative splicing. |
Mass spectrometry, co-immunoprecipitation, in vitro methylation assay, PI3K-AKT signaling readouts, transcriptome analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
30886105
|
| 2019 |
In the absence of PRMT1, increased PRMT6 specifically methylates FOXO3 at R188 and R249, activating FOXO3 and driving muscle atrophy through upregulation of autophagy markers and muscle-specific ubiquitin ligases. PRMT6 depletion abrogates FOXO3 hyperactivation in PRMT1-deficient muscle. |
Muscle-specific PRMT1 KO mice, adenovirus-delivered siRNA, in vitro methylation, site-directed mutagenesis, gene expression analysis |
Autophagy |
High |
30653406
|
| 2019 |
PPARα loss promotes colon carcinogenesis by increasing PRMT6 expression (via retinoblastoma protein depletion), and PRMT6 represses p27 expression through H3R2 dimethylation at its promoter. |
Intestine-specific Ppara KO mice, immunoblots, ChIP (implied by H3R2 dimethylation-mediated repression), colon cancer model |
Gastroenterology |
Medium |
31154022
|
| 2019 |
PRMT6 promotes alternate activation of tumor-associated macrophages via a non-catalytic interaction with ILF2, identifying macrophage migration inhibitory factor as a downstream target of PRMT6-ILF2 signaling. |
Proteomics, in vitro gain/loss-of-function, lung-targeted PRMT6 transgenic mouse, co-immunoprecipitation |
Molecular cancer research : MCR |
Medium |
31619507
|
| 2020 |
PRMT6 methylates CRAF at R100, and this methylation interferes with RAS/RAF binding, altering ERK-mediated PKM2 nuclear translocation and driving aerobic glycolysis (Warburg effect) in hepatocellular carcinoma. PRMT6 loss upregulates MFSD2A via reduced H3R2me2a, increasing docosahexaenoic acid levels. |
In vitro gain/loss-of-function, patient-derived organoids, PET-MRI animal models, PRMT6 KO HCC mouse model, transcriptome analysis |
Hepatology (Baltimore, Md.) |
High |
31469916
|
| 2020 |
H3R2me2a deposited by PRMT6 recruits the chromosomal passenger complex (CPC/Aurora B) to chromosome arms upon mitotic entry, facilitating H3S10 phosphorylation by Aurora B and chromosome condensation. In vitro, Aurora B preferentially binds H3 peptide containing H3R2me2a and phosphorylates H3S10. |
In vitro Aurora B binding and kinase assay with H3 peptides, cell-based CPC localization studies, ChIP, PRMT6 manipulation |
Nature communications |
High |
32001712
|
| 2020 |
PRMT6 methylates FOXO3 to regulate autophagy and protein degradation, and this is upstream of the PRMT1-PRMT6-FOXO3 axis; additionally PRMT6 is degraded by the F-box protein FBXO24 via polyubiquitination of K369, with the K369R mutant resistant to degradation. |
Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis, cell proliferation/migration assay |
Biochemical and biophysical research communications |
Medium |
32828318
|
| 2020 |
PRMT6 is also degraded via FBXW17-mediated polyubiquitination in a CSE-induced COPD context: FBXW17 selectively binds PRMT6 in nuclei and targets it for proteasomal degradation; proteasome inhibition or FBXW17 silencing abrogates PRMT6 loss. |
Co-immunoprecipitation, proteasome inhibitor treatment, siRNA knockdown, protein stability assay |
Frontiers in cell and developmental biology |
Medium |
33959602
|
| 2020 |
PRMT6 depletion in HCC cells increases PTEN and PI3K regulatory subunit p85 levels but decreases PDK1, causing AKT dephosphorylation and lung epithelial cell death; PRMT6 overexpression reverses CSE-induced cell death via PI3K/AKT signaling. |
PRMT6 KO and overexpression, Western blot for PI3K/AKT components, cell death/survival assays |
Aging |
Medium |
33260152
|
| 2020 |
PRMT6 deficiency in HCC promotes autophagy by preventing methylation of BAG5: PRMT6 physically interacts with and methylates BAG5, enhancing degradation of its partner HSC70 (an autophagy chaperone). Loss of PRMT6 stabilizes HSC70 and promotes autophagic flux. |
Co-immunoprecipitation, methylation assay, autophagy flux analysis, in vivo xenograft model |
Cancer letters |
Medium |
33186656
|
| 2020 |
PRMT6 is functionally redundant with CARM1 for H3R17me2a deposition: PRMT6 can deposit the H3R17me2a mark in vitro. CARM1/PRMT6 double KO embryos are smaller than CARM1 KO alone and MEFs show absence of mitotic H3R17me2a; combination inhibition of CARM1 and PRMT6 synergistically suppresses cell proliferation. |
In vitro methylation assay screen, double KO mouse genetics, MEF analysis, combination inhibitor treatment |
The Journal of biological chemistry |
High |
33008887
|
| 2021 |
PRMT6 methylates RCC1 (regulator of chromatin condensation 1) to promote RCC1 association with chromatin and activation of RAN GTPase, which is required for mitosis. CK2 phosphorylates and stabilizes PRMT6 through deubiquitylation. Disruption of CK2-PRMT6-RCC1 signaling causes mitotic defects and reduces GSC tumorigenicity. PRMT6 inhibitor EPZ020411 suppresses RCC1 methylation and enhances radiotherapy in brain tumor xenografts. |
Co-immunoprecipitation, in vitro methylation assay, MS, CK2 kinase assay, chromatin fractionation, xenograft model, PRMT6 inhibitor |
Molecular cell |
High |
33539787
|
| 2021 |
PRMT6 methylates huntingtin (HTT) at R118; without R118 methylation, HTT associates less with vesicles, anterograde axonal trafficking is diminished, and neuronal death occurs. Overexpressing PRMT6 restores axonal transport and neuronal viability in HD models; in HD flies overexpressing PRMT6 rescues axonal defects. |
In vitro methylation assay, site-directed mutagenesis, vesicle fractionation, live axonal transport imaging, HD fly model, HD cell model |
Cell reports |
High |
33852844
|
| 2021 |
LEF1 is an interaction partner of PRMT6, recruiting it to the CCND1 (Cyclin D1) promoter. Knockdown of LEF1 or PRMT6 reduces CCND1 expression and increases cells in G1 phase. |
Co-immunoprecipitation, ChIP, siRNA knockdown, cell cycle analysis, gene expression analysis |
Oncogenesis |
Medium |
34001852
|
| 2021 |
PRMT6 regulates widespread alternative splicing changes in NT2/D1 neural pluripotent cells primarily in an H3R2me2a-independent manner; only a small subset of PRMT6-dependent splicing events correlate with H3R2me2a at splice sites. |
PRMT6 KO, RNA-seq for splicing, H3R2me2a ChIP-seq comparison with splice site locations |
Life science alliance |
Medium |
39900436
|
| 2021 |
PRMT6 substrate recognition is broad with preference for RG motif (not RGG) and basic/bulky residues near the target arginine. PRMT6 methylates both R2 and R8 in the H3 tail peptide in vitro but H3R8 is not an in vivo substrate. |
Targeted mass spectrometry-based methylation assay with 204 amino acid substitutions in H3 peptide, in vitro methylation |
The FEBS journal |
High |
33764612
|
| 2022 |
PRMT6 methylates 6PGD at R324 to enhance its enzymatic activity, and methylates ENO1 at R9 (promoting active dimer formation) and R372 (promoting 2-PG substrate binding), thereby regulating oxidative pentose phosphate pathway and glycolysis in lung cancer cells. |
In vitro methylation assay, site-directed mutagenesis, enzymatic activity assays for 6PGD and ENO1, metabolic flux analysis |
Acta pharmaceutica Sinica. B |
Medium |
36815049
|
| 2022 |
IGF2BP2 stabilizes PRMT6 mRNA via m6A-mediated manner; PRMT6 catalyzes H3R2me2a to suppress MFSD2A expression; PRMT6 loss upregulates MFSD2A, increasing docosahexaenoic acid and impairing AML leukemia stem cell maintenance. |
m6A-seq/meRIP-seq, RNA-seq, genetic deletion, pharmacological inhibition, ChIP for H3R2me2a at MFSD2A promoter |
Cell stem cell |
High |
36574771
|
| 2022 |
PRMT6 functionally associates with PRMT5; H3R2me2a deposited by PRMT6 co-localizes with PRMT5-mediated H4R3me2s and H3R8me2s at promoters of CDKN2B and CCNG1, co-repressing these genes in colorectal cancer. PRMT5 was identified as a physical interaction partner of PRMT6 by mass spectrometry and co-IP. |
Mass spectrometry, co-immunoprecipitation, GST pulldown, RNA-seq, ChIP, siRNA knockdown |
Experimental cell research |
Medium |
36400182
|
| 2023 |
PRMT6 asymmetrically dimethylates STAT3 at R729 (STAT3 R729me2a), which is required for STAT3 membrane localization, interaction with JAK2, Y705 phosphorylation, and PRMT6-driven breast cancer cell metastasis. |
Co-immunoprecipitation, in vitro methylation assay, site-directed mutagenesis, subcellular fractionation, in vivo metastasis assay, PRMT6 inhibitor |
Cell death & disease |
Medium |
37813837
|
| 2023 |
PRMT6 maintains CDC20 transcription via H3R2me2a; CDC20 then interacts with and promotes proteasomal degradation of CDKN1B (p27), driving GBM cell proliferation. This PRMT6-CDC20-CDKN1B axis was confirmed by rescue experiments. |
ChIP, co-immunoprecipitation, knockdown/rescue experiments, cell cycle analysis, ubiquitination assay |
Oncogene |
Medium |
36792756
|
| 2023 |
LSD1 and PRMT6 are overexpressed in an androgen-dependent manner in skeletal muscle of SBMA patients/mice, cooperatively and synergistically transactivate androgen receptor, and their effect is enhanced by expanded polyQ. miRNA-mediated co-silencing of LSD1 and PRMT6 attenuates disease in SBMA mice. |
Patient/mouse tissue analysis, cell lines, co-transactivation assays, SBMA fly model, miRNA-mediated silencing in SBMA mice |
Nature communications |
Medium |
36746939
|
| 2023 |
PRMT6 forms a transcription-repressive complex with PARP1 and CRL4B at the PER3 circadian clock gene promoter; genome-wide analysis shows PRMT6/PARP1/CUL4B co-occupy genes involved in circadian rhythms to promote breast cancer proliferation and metastasis. |
Co-immunoprecipitation, ChIP-seq, reporter assays, PARP1 inhibitor treatment |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
36941223
|
| 2024 |
PRMT6 methylates STING, inactivating it and reducing TBK1 and IRF3 phosphorylation, thereby diminishing type I interferon production and antiviral innate immunity in HSV-1 infection. |
PRMT6 KO mice, in vitro methylation assay, co-immunoprecipitation, phosphorylation assays, viral load measurement, PRMT6 inhibitor administration |
Brain : a journal of neurology |
Medium |
38366606
|
| 2024 |
PRMT6 interacts with STAT1 to jointly regulate ACSL1 transcription; PRMT6 reduction in diabetic nephropathy induces lipid peroxidation by upregulating ACSL1, contributing to ferroptosis. STAT1 inhibition with fludarabine delays DN progression. |
PRMT6 KO mice, transcriptomic/lipidomic analysis, co-immunoprecipitation, ChIP, pharmacological STAT1 inhibition |
Cell death and differentiation |
Medium |
39134684
|
| 2024 |
PRMT6 methylates AMPKα1 at R403; PRMT6 directly interacts with and methylates AMPKα1 in vitro without other cellular components. PRMT6-mediated methylation promotes AMPKα1 phase separation and puncta formation in cells. |
In vitro methylation assay, co-immunoprecipitation, truncated/point mutant analysis, immunocytochemistry |
Biochemical and biophysical research communications |
Medium |
37178510
|
| 2024 |
PRMT6 methylates ALKBH5 at R283, which inhibits Indisulam-induced ubiquitination and proteasomal degradation of RBM39, increases RBM39 levels, and promotes alternative splicing of proto-oncogenes, driving Indisulam resistance in NSCLC. |
In vitro methylation assay, co-immunoprecipitation, ubiquitination assay, RNA-seq for splicing, xenograft model, PRMT6 inhibitor (MS023) |
PLoS biology |
Medium |
40465651
|
| 2024 |
PRMT6 mediates p62 asymmetric dimethylarginine (ADMA) modification, increasing p62 oligomerization and phase separation, promoting p62 body formation that sequesters Keap1 to activate Nrf2 signaling, forming a negative feedback loop during ferroptosis. |
Co-immunoprecipitation, proximal ligation assay, FRAP for phase separation, in vitro methylation, xenograft model |
Theranostics |
Medium |
38994016
|
| 2024 |
PRMT6 forms a coactivation complex with NF-κB and catalyzes H3R17 asymmetric dimethylation at the Ccl2 promoter in macrophages, transcriptionally upregulating CCL2 to amplify macrophage chemotactic signaling and heterotopic ossification. |
ChIP, co-immunoprecipitation, macrophage-specific PRMT6 KO mice, CCL2 supplementation rescue, HO mouse model |
Bone research |
Medium |
41803087
|
| 2024 |
PRMT6 directly methylates ALKBH5 at R283, which promotes breast tumor growth; methylation of ALKBH5 by PRMT6 increases LDHA RNA stability via m6A demethylation, leading to increased aerobic glycolysis. Confirmed in PRMT6-KO mice. |
In vitro methylation assay, PRMT6 KO mice, m6A analysis, RNA stability assay, glycolysis measurement |
Frontiers of medicine |
Medium |
38466502
|
| 2024 |
PRMT6 inhibits TRAF6 transcription via H3R2me2a at the TRAF6 promoter, reducing TRAF6-EZH2 interaction and enhancing EZH2 protein stability, thereby promoting glioblastoma invasion and migration. |
ChIP, co-immunoprecipitation, ubiquitination assay, knockdown/overexpression, xenograft model |
Cell death & disease |
Medium |
39043634
|
| 2024 |
Prmt6 deficiency reduces H3R2me2a at promoters of Ppard, Acox3, and Cpt1a (fatty acid oxidation genes), increasing chromatin accessibility and shifting osteoclast metabolism toward fatty acid oxidation rather than glycolysis, thereby suppressing osteoclastogenesis. |
PRMT6 KO mice (OVX model), ATAC-seq, ChIP for H3R2me2a, metabolic assays, PRMT6 inhibitor |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
39120025
|
| 2024 |
PRMT6 interacts with HIF-1α and methylates it, increasing HIF-1α protein stability, thereby promoting glycolysis and neuroinflammation in spinal cord microglia and exacerbating neuropathic pain. |
Co-immunoprecipitation, protein stability assay, PRMT6 KO/knockdown/overexpression, glycolysis and inflammation assays, in vivo CCI mouse model |
Brain, behavior, and immunity |
Medium |
38402915
|
| 2024 |
A chimeric PRMT6 protein (PRMT6MT2B2) formed by an endogenous retroviral LTR promoter increases H2AR3me2a but not H4R3me2a (unlike canonical PRMT6 which increases both), and promotes epiblast cell fate in mouse preimplantation embryos when expressed in one blastomere. |
Overexpression in fibroblasts and mouse two-cell embryos, histone modification Western blot, blastocyst lineage analysis |
Biology of reproduction |
Medium |
38196172
|
| 2025 |
Metformin directly binds PRMT6 and inhibits its H3R2 methylation activity, thereby enhancing chromatin association of UHRF1, promoting DNA methylation, repressing DNA replication-associated genes, and inducing cell cycle arrest in breast cancer cells. Genetic disruption of metformin-PRMT6 interaction attenuates metformin's inhibitory effect. |
Direct binding assay, in vitro methylation inhibition, UHRF1 chromatin fractionation, DNA methylation analysis, cell cycle analysis, xenograft model |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
41327885
|
| 2025 |
PRMT6 mono-methylates c-MYC at R371, inhibiting its poly-ubiquitination and proteasomal degradation, thereby stabilizing c-MYC protein and promoting colorectal cancer cell proliferation. |
In vitro methylation assay, co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis, xenograft model |
Journal of translational medicine |
Medium |
39819457
|
| 2024 |
A GATA1 frameshift mutation enhances its recruitment of PRMT6, which deposits H3R2me2a at GATA1 target gene regulatory elements, repressing transcription and impairing erythroid differentiation; PRMT6 inhibitor MS023 partially rescues impaired erythroid differentiation. |
Proximity labeling/mass spectrometry, co-immunoprecipitation, ChIP, PRMT6 inhibitor treatment, erythroid differentiation assay |
Haematologica |
Medium |
38385251
|
| 2020 |
The first cocrystal structure of PRMT6 bound to a covalent inhibitor (MS117) was solved, confirming covalent binding mode by mass spectrometry and kinetic studies. The structure reveals the binding mode of a cysteine-reactive compound distinct from reversible PRMT inhibitors. |
X-ray cocrystal structure, mass spectrometry, kinetic analysis, selectivity profiling |
Journal of medicinal chemistry |
High |
32367723
|