PRMT2 promotes dextran sulfate sodium-induced colitis by inhibiting SOCS3 via histone H3R8 asymmetric dimethylation
Background and purpose: There is emerging evidence for the critical roles of epigenetic modifiers in the development of inflammatory bowel disease (IBD).
Protein arginine methyltransferase 2 (PRMT2) is responsible for the methylation of arginine residues on histones and targets transcription factors critically involved in many cellular processes, including gene transcription, mRNA splicing, cell proliferation, and differentiation.
However, its role in colitis remains unknown. In this study, the role and underlying mechanisms of PRMT2 in colitis was studied.
Experimental approach: A mouse dextran sulfate sodium (DSS)-induced experimental colitis model was applied to study PRMT2 in colitis. Lentivirus-induced PRMT2 silencing or overexpression in vivo was applied to address the role of PRMT2 in colitis. Detailed western blot and expression analysis was done to understand epigenetic changes induced by PRMT2 in colitis.
Key results: PRMT2 is highly expressed in patients with IBD, inflamed colon of mice, and TNF-α stimulated mice gut epithelial cells. PRMT2 overexpression aggravates while knockdown alleviates DSS-induced colitis in mice, suggesting that PRMT2 is a pivotal mediator of colitis development.
Mechanistically, PRMT2 mediates colitis by increasing repressive histone mark H3R8 asymmetric methylation (H3R8me2a) at the promoter region of the suppressor of cytokine signaling 3 (SOCS3) promoter.
Resultant inhibition of SOCS3 expression and SOCS3-mediated degradation of TNF receptor-associated factor 5 (TRAF5) via ubiquitination led to elevated TRAF5 expression and TRAF5-mediated downstream NF-κB/MAPK activation.
Conclusion and implications: Our study demonstrates that PRMT2 acts as a transcriptional co-activator for proinflammatory genes during colitis. Hence targeting PRMT2 may provide a novel therapeutic approach for colitis.
PRMT2 accelerates tumorigenesis of hepatocellular carcinoma by activating Bcl2 via histone H3R8 methylation
Protein arginine methyltransferases (PRMTs) have been implicated in the development of various cancers.
PRMT2, a member of the type I PRMT family, is overexpressed in multiple tumors.
However, the expression and role of PRMT2 in hepatocellular carcinoma (HCC) have not been studied.
Here, we discovered that PRMT2 expression is elevated in HCC tissues compared to the corresponding nontumor tissues, and PRMT2 overexpression is an independent predictor of poor prognosis in HCC patients.
Depletion of PRMT2 in HCC cell lines inhibited their cell growth and induced apoptosis. Mechanistic investigations showed that PRMT2 is responsible for H3R8 asymmetric methylation (H3R8me2a).
H3R8me2a enrichment at the Bcl2 promoter increases its accessibility to STAT3, promoting Bcl2 gene expression.
In addition, our results confirmed that the catalytically inactive mutant of PRMT2 or the type I PRMT inhibitor MS023 impaired the pro-tumorigenic functions of PRMT2 in HCC cells.
Overall, our findings showed that PRMT2 functions as an oncogenic gene in HCC, revealing its potential as a novel therapeutic target in HCC.
PRMT2 links histone H3R8 asymmetric dimethylation to oncogenic activation and tumorigenesis of glioblastoma.
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.
The histone demethylase Kdm6b regulates subtype diversification of mouse spinal motor neurons during development
How a single neuronal population diversifies into subtypes with distinct synaptic targets is a fundamental topic in neuroscience whose underlying mechanisms are unclear.
Here, we show that the histone H3-lysine 27 demethylase Kdm6b regulates the diversification of motor neurons to distinct subtypes innervating different muscle targets during spinal cord development.
In mouse embryonic motor neurons, Kdm6b promotes the medial motor column (MMC) and hypaxial motor column (HMC) fates while inhibiting the lateral motor column (LMC) and preganglionic motor column (PGC) identities. Our single-cell RNA-sequencing analyses reveal the heterogeneity of PGC, LMC, and MMC motor neurons.
Further, our single-cell RNA-sequencing data, combined with mouse model studies, demonstrates that Kdm6b acquires cell fate specificity together with the transcription factor complex Isl1-Lhx3.
Our study provides mechanistic insight into the gene regulatory network regulating neuronal cell-type diversification and defines a regulatory role of Kdm6b in the generation of motor neuron subtypes in the mouse spinal cord.
Role of p300, a histone acetyltransferase enzyme, in osteoblast differentiation
Bone is a dynamic and tough connective tissue that undergoes constant remodeling throughout life.
Bone-forming osteoblasts respond to various hormones, cytokines, and growth factors, and synthesize extracellular matrix components.
Runx2 (Runt-related transcription factor 2), a bone transcription factor, is essential for ossification by stimulating the expression of osteoblast differentiation marker genes, including type I collagen, alkaline phosphatase, and osteocalcin.
Coactivators, such as p300, CBP (CREB-binding protein), and PCAF (p300/CBP associated factor) tightly regulate osteoblast differentiation via Runx2.
There is growing evidence indicating the role of p300, which possesses histone acetyltransferase (HAT) activity, in regulating histones and transcription factors such as Runx2 during osteoblast differentiation.
In this review, we aim to delineate the role of p300 at the molecular level, emphasizing the importance of its HAT activity during osteoblast differentiation.
Furthermore, this review intends to highlight the regulation of p300 at multiple levels, including post-translational and ncRNAs, that might exert an indirect influence on bone formation.
Histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit exacerbates inflammation in depression rats by modulating microglia polarization
Depression is a major cause of emotional agony and degraded living quality. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is involved in histone methylation in human diseases.
This experiment was designed to investigate the mechanism of EZH2 on depression.
The Depression rat model was established via the treatment of chronic unpredictable mild stress (CUMS) to identify rat depression-like behaviors. EZH2 expression was determined and then silenced to assess its effect on depression-like behaviors and neuroinflammation.
Microglia were isolated, cultured, identified and activated to assess EZH2 expression. Effect of EZH2 on microglia polarization was evaluated.
Next, the binding relation between microRNA (miR)-29b-3p and EZH2 or matrix metallopeptidase 2 (MMP2) was analyzed.
Levels of miR-29b-3p expression and MMP2 transcription were examined. Additionally, the role of miR-29b-3p in microglia polarization was tested.
Depression-like behaviors were exhibited after CUMS induction. EZH2 was overexpressed in CUMS-treated rats and lipopolysaccharide (LPS)-induced microglia. EZH2 silencing reversed depression-like behaviors. EZH2 silencing mitigated inflammation in depression by manipulating microglia M2-type polarization. EZH2 targeted miR-29b-3p expression to promote MMP2 transcription.
Histone H3R8 Monomethyl (H3R8me1) Polyclonal Antibody |
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| A-3715 | EpiGentek |
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Histone H3R8 Methylation Antibody Panel Pack |
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| C10016 | EpiGentek |
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Histone H3R8 Dimethyl Symmetric (H3R8me2s) Polyclonal Antibody |
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| A-3706 | EpiGentek |
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Histone H3R8 Dimethyl Asymmetric (H3R8me2a) Polyclonal Antibody |
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| A-3716 | EpiGentek |
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EpiQuik Global Di-Methyl Histone H3R8 Quantification Kit (Colorimetric) |
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| P-3096 | EpiGentek |
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Histone H3R26me1 Antibody |
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| ABD7220 | Lifescience Market | 100 ug | 525.6 EUR |
Histone H3R17me1 Antibody |
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| 20-abx000025 | Abbexa |
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Histone H3R26me1 Antibody |
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| 20-abx000034 | Abbexa |
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Histone H3R17me1 Antibody |
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| CSB-PA874736- | Cusabio | each | 402 EUR |
Histone H3R17me1 Antibody |
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| CSB-PA874736-100ul | Cusabio | 100ul | 456 EUR |
Histone H3R26me1 Antibody |
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| CSB-PA725874- | Cusabio | each | 402 EUR |
Inhibition of miR-29b-3p reversed the role of EZH2 silencing in microglia M2-type polarization and promoted inflammation.
EZH2 inhibited miR-29b-3p expression by combining with miR-29b-3p promoter and trimethylation of histone H3-lysine 27-trimethylated upregulation, and then elevated MMP2 transcription and triggered microglia M1-type polarization, thus exacerbating depression-like behaviors and neuroinflammation of depression.