Profile of Histone H3 Lysine 4 Trimethylation and the Effect of Lipopolysaccharide/Immune Complex-Activated Macrophages on Endotoxemia

Ruenjaiman, Vichaya; Butta, Patcharavadee; Leu, Yu-Wei; Pongpanich, Monnat; Leelahavanichkul, Asada; Kueanjinda, Patipark; Palaga, Tanapat

doi:10.3389/fimmu.2019.02956

Cited by 16 publications

(15 citation statements)

References 44 publications

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“…Active gene loci are characterized by a combination of all three methylated forms of H3K4 and H3K4me, and H3K4me2 are found at both transcriptionally active promoters and distal regulatory elements and are considered activating signals [72][73][74][75]. Both H3K4me3 and H3K27me3 play an essential role in the polarization and activation of immune cells, including CD8 T cells [76][77][78][79][80][81]. We found repressive K27me3 on nine different H3 proteoforms combined with many other PTMs (Figure 3D).…”

Section: Differences In Effector T Cell Histone Modification From the Spleen Lung And Bronchial Lavagementioning

confidence: 80%

Mapping Influenza-Induced Posttranslational Modifications on Histones from CD8+ T Cells

Rezinciuc

Tian

et al. 2020

Viruses

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T cell function is determined by transcriptional networks that are regulated by epigenetic programming via posttranslational modifications (PTMs) to histone proteins and DNA. Bottom-up mass spectrometry (MS) can identify histone PTMs, whereas intact protein analysis by MS can detect species missed by bottom-up approaches. We used a novel approach of online two-dimensional liquid chromatography-tandem MS with high-resolution reversed-phase liquid chromatography (RPLC), alternating electron transfer dissociation (ETD) and collision-induced dissociation (CID) on precursor ions to maximize fragmentation of uniquely modified species. The first online RPLC separation sorted histone families, then RPLC or weak cation exchange hydrophilic interaction liquid chromatography (WCX-HILIC) separated species heavily clad in PTMs. Tentative identifications were assigned by matching proteoform masses to predicted theoretical masses that were verified with tandem MS. We used this innovative approach for histone-intact protein PTM mapping (HiPTMap) to identify and quantify proteoforms purified from CD8 T cells after in vivo influenza infection. Activation significantly altered PTMs following influenza infection, histone maps changed as T cells migrated to the site of infection, and T cells responding to secondary infections had significantly more transcription enhancing modifications. Thus, HiPTMap identified and quantified proteoforms and determined changes in CD8 T cell histone PTMs over the course of infection.

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Section: Differences In Effector T Cell Histone Modification From the Spleen Lung And Bronchial Lavagementioning

confidence: 80%

Mapping Influenza-Induced Posttranslational Modifications on Histones from CD8+ T Cells

Rezinciuc

Tian

et al. 2020

Viruses

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“…This includes probing major histone modifications like H3K4me3, a histone mark that is accumulated in the promoter region of pro-inflammatory genes upon LPS activation. 163 At the same time, it is also absolutely crucial to explore the role of other nuclear envelope (NE) proteins in order to develop a more complete picture of the regulatory landscape by which macrophage activation is regulated by alterations of the NE, thus tuning the balance between pro-inflammatory and pro-healing macrophages.…”

Section: Macrophage Polarization Induces Changes In Nuclear Morpholog...mentioning

confidence: 99%

Mechanoimmunology: Are inflammatory epigenetic states of macrophages tuned by biophysical factors?

2022

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Many inflammatory diseases that are responsible for a majority of deaths are still uncurable, in part as the underpinning pathomechanisms and how to combat them is still poorly understood. Tissue-resident macrophages play pivotal roles in the maintenance of tissue homeostasis, but if they gradually convert to proinflammatory phenotypes, or if blood-born proinflammatory macrophages persist long-term after activation, they contribute to chronic inflammation and fibrosis. While biochemical factors and how they regulate the inflammatory transcriptional response of macrophages have been at the forefront of research to identify targets for therapeutic interventions, evidence is increasing that physical factors also tune the macrophage phenotype. Recently, several mechanisms have emerged as to how physical factors impact the mechanobiology of macrophages, from the nuclear translocation of transcription factors to epigenetic modifications, perhaps even DNA methylation. Insight into the mechanobiology of macrophages and associated epigenetic modifications will deliver novel therapeutic options going forward, particularly in the context of increased inflammation with advancing age and age-related diseases. We review here how biophysical factors can co-regulate pro-inflammatory gene expression and epigenetic modifications and identify knowledge gaps that require urgent attention if this therapeutic potential is to be realized.

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“…Histone H3 trimethylation on lysine 4 (H3K4me3) and 27 (H3K27me3) has been significantly correlated with macrophage differentiation [40]. In mouse model, M1 showed decreased global enrichment of H3K4me3 whereas M2 increased enrichment of H3K4me3 [41]. As CovS-miR-3 inhibited lysine methyltransferase 2C (KMT2C) with miR-373-3p, miR-372-3p, miR-302d-3p, miR-302a-3p, miR-520e, miR-520c-3p and miR-520b (Figure 4), H3K4me3 would be decreased by BNT162b2 vaccination, which may induce M1 state of macrophages.…”

Section: A Balance Of Reactogenicity and Immunogenicity By Covs-mir-3mentioning

confidence: 99%

Quantum microRNA Assessment of COVID-19 RNA Vaccine: Hidden Potency of BNT162b2 SASR-CoV-2 Spike RNA as MicroRNA Vaccine

Fujii¹

2021

AICS

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Objective: The pandemic of coronavirus disease 2019 (COVID-19) is caused by infection with severe respiratory syndrome human coronavirus 2 (SARS-CoV-2). The spike (S) RNA of SARS-CoV-2 is used to build the COVID-19 vaccine. Although the level of immune response elicited by the full-length S RNA vaccine and the Receptor Binding Domain (RBD) vaccine that is a part of S is similar, the full-length S RNA vaccine is safer and lower reactogenicity than the RBD vaccine. However, the reason has not yet been clarified. On the other hand, the COVID-19 RNA vaccine with the S sequences may produce viral microRNAs (miRNAs). But there are no miRNA assessments for the safety of the COVID-19 vaccines. Therefore, evaluation as miRNA vaccines is necessary for risk management of vaccination.Materials and Methods: miRNA Fold was used for pre-miRNA prediction in SARS-CoV-2 S RNA. MRmicro-T was used for protein target search. The integrated network algorithm as the miRNA entangling sorter (METS) analysis by using quantum miRNA language plus Artificial Intelligence (AI) were used as previously described. Results:In computation, sixteen SARS-CoV-2-S-derived miRNAs bound to the negative strand S RNA with quite strong avidities. Further, CovS-miR-21 downregulated Rho associated coiled-coil containing protein kinase (ROCK2) and aryl hydrocarbon receptor nuclear translocator like (ARNTL), and CovS-miR-3 decreased lysine methyltransferase 2C (KMT2C). Therefore, in the METS analysis, CovS-miR-21 suppressed the function of Ras homolog family member A (RhoA)/Rock2 signaling and circadian rhythm, and CovS-miR-3 inhibited histone H3-K4 methylation. Conclusion:We found that BNT162b2 inhibits SARS-CoV-2 replication through degradation of negative strand viral RNAs that are completely paired with SARS-CoV-2 S-derived miRNAs. Further, CovS-miR-21 derived from BNT162b2 restores circadian rhythm and attenuate immunogenicity. Quantum miRNA assessments showed that the BNT162b2 RNA vaccine has a character of miRNA vaccine and is an excellent vaccine with high efficacy and low side-effects.

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Profile of Histone H3 Lysine 4 Trimethylation and the Effect of Lipopolysaccharide/Immune Complex-Activated Macrophages on Endotoxemia

Cited by 16 publications

References 44 publications

Mapping Influenza-Induced Posttranslational Modifications on Histones from CD8+ T Cells

Mapping Influenza-Induced Posttranslational Modifications on Histones from CD8+ T Cells

Mechanoimmunology: Are inflammatory epigenetic states of macrophages tuned by biophysical factors?

Quantum microRNA Assessment of COVID-19 RNA Vaccine: Hidden Potency of BNT162b2 SASR-CoV-2 Spike RNA as MicroRNA Vaccine

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