H3K4me3-marked histone orchestrates neutrophil plasticity from immunity to tissue regeneration
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ABSTRACT:
PROVIDER: PRJNA774257 | ENA |
REPOSITORIES: ENA
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Project description:In this study, we used chromatin immunoprecipitation sequencing (ChIP-Seq) analysis of histone H3K4me3-marked, to identify various TSSs associated with LPS-, TNF-alfa- and IL-10-stimulated neutrophils from healthy individuals, as well as neutrophils derived from the patients with sepsis (systemic septic inflammation with LPS-stimulated neutrophils), NMOSD (aseptic inflammation with neutrophils pre-activated by TNF-alfa and periodontitis (localized self-limiting septic inflammation with IL-10-positive neutrophils). We provided comprehensive epigenomic analysis within H3K4me3- marked histone that allowed us to identify human neutrophil regulators affecting their plasticity during inflammation as well as suppression.
2021-10-27 | GSE186508 | GEO
Project description:Neutrophils are a heterogenous population capable of both antimicrobial functions and suppressor ones, however, no specific pattern of transcription factors controlling this plasticity has been identified. We observed rapid changes in the neutrophil status after stimulation with LPS, pre-activating concentration of TNF-α, or IL-10. Chromatin immunoprecipitation sequencing (ChIP-Seq) analysis of histone H3K4me3 allowed us to identify various transcriptional start sites (TSSs) associated with plasticity and heterogeneity of human neutrophils. Gene Ontology analysis demonstrated great variation within target genes responsible for neutrophil activation, cytokine production, apoptosis, histone remodelling as well as NF-κB transcription factor pathways. These data allowed us to assign specific target genes positioned by H3K4me3-marked histone with a different pattern of gene expression related to NF-κB pathways, apoptosis, and a specific profile of cytokines/chemokines/growth factors realised by neutrophils stimulated by LPS, IL-10, or TNF-α. We discovered IL-10-induced apoptotic neutrophils being transcriptionally active cells capable of switching the profile of cytokines/chemokines/growth factors desired in resolving inflammation via non-canonical NF-κB pathway with simultaneous inhibition of canonical NF-κB pathway. As apoptotic/suppressive neutrophils induced by IL-10 via positioning genes within H3K4me3-marked histone were transcriptionally active, newly described DNA binding sites can be considered as potential targets for immunotherapy.H3K4me3 histone ChIP-Seq analysis reveals molecular drivers critical for switching neutrophils from their pro- to anti-inflammatory properties.
| S-EPMC9229595 | biostudies-literature
Project description:Macrophage-Endothelial Cell Crosstalk Orchestrates Neutrophil Recruitment in Inflamed Mucosa scRNA-Seq
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Project description:Macrophage-Endothelial Cell Crosstalk Orchestrates Neutrophil Recruitment in Inflamed Mucosa RNA-Seq
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Project description:Age-dependent cell stemness plasticity orchestrates postnatal functional maturity of ruminants
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Project description:In this study, we demonstrated dysregulation of DNA transcription in H3K4me3 histone in circulating neutrophils of HIV-infected subjects. Chromatin immunoprecipitation sequencing (ChIPseq) H3K4me3 histone analysis revealed that the most spectacular abnormalities were observed in the exons, introns and promoter-TSS regions. Bioinformatic analysis of Gene Ontology, including biological processes, molecular function and cellular components, demonstrated that the main changes were related to the genes responsible for cell activation, cytokine production, adhesive molecule expression, histone remodeling via upregulation of methyltransferase process and downregulation of NF-kB transcription factor in canonical pathways. Abnormalities within H3K4me3 implicated LPS-mediated NF-kB canonical activation pathway that was a result of low amounts of kB DNA sites within histone H3K4me3, low NF-kB (p65 RelA) and TLR4 mRNA expression as well as reduced free NF-kB (p65 RelA) accumulation in the nucleus. ‘Panoramic view of the landscape gene’ within histone H3K4me3 led us postulate that impairment within the canonical NF-kB cell activation pathway may be the primary phenomenon responsible for neutrophil dysfunction observed in HIV-infected individuals
2021-03-23 | GSE169310 | GEO
Project description:Background: Severe septic syndromes deeply impair innate and adaptive immunity. While neutrophils represent the first line of defense against infection, little is known about their phenotype and functions during sepsis-induced immunosuppression. The objective of this study was thus to perform for the first time a global evaluation of neutrophil alterations in immunosuppressed septic patients based on phenotypic, functional and transcriptomic studies. In addition, the potential association of these parameters and deleterious outcomes was assessed. Methods: Peripheral blood was collected from 9 septic shock patients at D3-4 and D6-8 presenting with features of sepsis-induced immunosuppression and compared to 8 healthy controls. Results: In order to get on overview of potential neutrophil alterations after sepsis, we performed transcriptomic analyses on purified neutrophils from 9 septic shock patients and 8 healthy volunteers. For each time point, comparisons were made between patients and controls. Venn diagrams indicated that 364 up-regulated genes and 328 down-regulated genes were common between the two analyses (Supplementary Tables 1 and 2). Interestingly, most of the differentially expressed genes are involved in cell maturation (CD177), apoptosis (STK4, Caspase 8), cell recruitment and chemotaxis (CD44, TPST, MMP9, CREB1), and antimicrobial properties (ARG1, STOM, ADAM9, CD63, YKL40) of neutrophils. Conclusions: The aim of the current study was to perform an extensive investigation of neutrophil alterations during sepsis-induced immunosuppression through phenotypic, functional and transcriptomic studies. Notably, transcriptomic study on purified neutrophils revealed differentially expressed genes between septic patients and healthy volunteers.
2015-12-28 | GSE64457 | GEO
Project description:Microrchidia (MORC) proteins are GHKL ATPases that function in gene silencing in multiple organisms. Animal MORCs also contain CW-type zinc finger domains, which are known to bind to modified histones. We identified mouse MORC3 in a mutant screen for factors required for transgene silencing. We also found that MORC3 localizes to promoters marked by H3K4 trimethylation (H3K4me3) throughout the genome, consistent with its binding to H3K4me3 in vitro. We solved the crystal structure of the MORC3 ATPase-CW domain bound to the nucleotide analog AMPPNP and in complex with a H3K4me3 peptide. The CW domain uses an aromatic cage to bind trimethylated Lys4 and forms extensive hydrogen bonds with the H3 tail. We used native mass spectrometry to show that this region forms ATP dependent dimers, and that dimer formation is enhanced in the presence of non-hydrolyzable ATP analogs. Our work sheds light on aspects of the molecular function of MORC3 and suggests a counterintuitive role of MORC3 in both binding to active promoters and regulating gene silencing.
2016-08-15 | GSE78258 | GEO
Project description:PROX1 Orchestrates Tumor Metabolic Plasticity by Integrating LKB1-AMPK Signaling with BCAA Catabolism
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Project description:We previously mapped ETV1 using ChIP-Seq in GIST48 cells (GSE22441). Here, we map the enhancer landscape marked by histone H3K4me1 and the promoter landscape marked by histone H3K4me3 in GIST48 cells. Crosslink ChIP-Seq of H3K4me1 and H3K4me3 in GIST48 cells
2015-01-01 | E-GEOD-64609 | biostudies-arrayexpress