NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils
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PROVIDER: PRJNA1008263 | ENA |
REPOSITORIES: ENA
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Project description:Neutrophil extracellular traps (NETs) counteract bacterial and fungal pathogens but can also promote thrombosis, autoimmunity, and sterile inflammation. The presence of citrullinated histones, generated by the peptidylarginine deiminase 4 (PAD4), is synonymous with NETosis and is considered independent of apoptosis. Mitochondrial- and death receptormediated apoptosis promote GSDME-dependent calcium mobilization and membrane permeabilization leading to histone H3 citrullination (H3Cit), nuclear DNA extrusion, and cytoplast formation. H3Cit is concentrated at the promoter in bone marrow neutrophils, and redistributes in a coordinated process from promoter to intergenic and intronic regions during apoptosis. Loss of GSDME prevents nuclear and plasma membrane disruption of apoptotic neutrophils, but prolongs early apoptosis-induced cellular changes to the chromatin and cytoplasmic granules. Apoptotic signaling engages PAD4 in neutrophils, establishing a cellular state that is primed for NETosis, but that occurs only upon membrane disruption by GSDME, thereby redefining the end-of-life for neutrophils.
2023-12-27 | GSE241485 | GEO
Project description:This experiment was designed to identify transcripts which are changed in plants deficient for evolutionary conserved EST1B gene. A mutation in est1b leads to a constitutive up-regulation of a PAD4-dependent pathogen response pathway. To eliminate secondary effects of the constitutive pathogen response in est1b mutants we will analyze transcriptoms in plants in which lack PAD4. Keywords: Expression profilling by array
2009-11-18 | GSE18979 | GEO
Project description:This experiment was designed to identify transcripts which are changed in plants deficient for evolutionary conserved EST1B gene. A mutation in est1b leads to a constitutive up-regulation of a PAD4-dependent pathogen response pathway. To eliminate secondary effects of the constitutive pathogen response in est1b mutants we will analyze transcriptoms in plants in which lack PAD4. Keywords: Expression profilling by array 6 samples were used in this experiment
2009-11-17 | E-GEOD-18979 | biostudies-arrayexpress
Project description:Neutrophil extracellular trap (NET) formation can generate short-term, functional anucleate cytoplasts and trigger loss of cell viability. We demonstrated that the necroptotic cell death effector mixed lineage kinase domain-like (MLKL) translocated from the cytoplasm to the plasma membrane and stimulated downstream NADPH oxidase-independent ROS production, loss of cytoplasmic granules, breakdown of the nuclear membrane, chromatin decondensation, histone hypercitrullination, and extrusion of bacteriostatic NETs. This process was coordinated by receptor-interacting protein kinase-1 (RIPK1), which activated the caspase-8-dependent apoptotic or RIPK3/MLKL-dependent necroptotic death of mouse and human neutrophils. Genetic deficiency of RIPK3 and MLKL prevented NET formation but did not prevent cell death, which was because of residual caspase-8-dependent activity. Peptidylarginine deiminase 4 (PAD4) was activated downstream of RIPK1/RIPK3/MLKL and was required for maximal histone hypercitrullination and NET extrusion. This work defines a distinct signaling network that activates PAD4-dependent NET release for the control of methicillin-resistant Staphylococcus aureus (MRSA) infection.
| S-EPMC6301070 | biostudies-literature
Project description:We found PAD4, which is one of the transcriptional co-regulator by histone modification, was highly expressed in lineage-, Sca-1+, c-kit+ (termed as LSK) cells of mouse bone marrow. To find the target genes which are regulated by PAD4 in LSK cells, we analyzed gene expression in PAD4-deficient mouse as compared with wild-type mouse. Gene expression in wild-type and PAD4-deficient LSK cells
2013-06-01 | E-GEOD-45482 | biostudies-arrayexpress
Project description:We found PAD4, which is one of the transcriptional co-regulator by histone modification, was highly expressed in lineage-, Sca-1+, c-kit+ (termed as LSK) cells of mouse bone marrow. To find the target genes which are regulated by PAD4 in LSK cells, we analyzed gene expression in PAD4-deficient mouse as compared with wild-type mouse.
2013-06-01 | GSE45482 | GEO
Project description:Gene expression profiling leading to the identification of novel components in the EDS1/PAD4-regulated defence pathway
2006-02-15 | E-MEXP-546 | biostudies-arrayexpress
Project description:Neutrophil extracellular trap (NET) formation has emerged as an important response against various pathogens; it also plays a role in chronic inflammation, autoimmunity, and cancer. Despite a growing understanding of the mechanisms underlying NET formation, much remains to be elucidated. We previously showed that in human neutrophils activated with different classes of physiological stimuli, NET formation features both early and late events that are controlled by discrete signaling pathways. However, the nature of these events has remained elusive. We now report that PAD4 inhibition only affects the early phase of NETosis, as do distinct signaling intermediates (TAK1, MEK, p38 MAPK). Accordingly, the inducible citrullination of residue R2 on histone H3 is an early neutrophil response that is regulated by these kinases; other arginine residues on histones H3 and H4 do not seem to be citrullinated. Conversely, chromatin decondensation is a belated event in NET formation, that is impaired by the inhibition of most signaling pathways known to control the phenomenon. We additionally show that neutrophils can condition themselves to be poised for rapid NET formation, and that this represents another late process. Similarly, activated neutrophils release a number of endogenous proteic factors that promote and largely mediate NET generation, and this is yet another late process. Our data shed new light on the cellular processes underlying NET formation, and unveil some unsuspected facets of the phenomenon. In view of the involvement of NETs in both homeostasis and several pathologies, our findings are of broad relevance.
2021-10-12 | PXD027055 | Pride
Project description:Arabidopsis Enhanced Disease Susceptibility 1 (EDS1) and its direct partner Phytoalexin Deficient 4 (PAD4) are required for both basal resistance against virulent pathogens and innate immune responses mediated by all tested TIR (Toll-Interleukin-1 Receptors) type nucleotide-binding/leucine-rich-repeat (NLR) receptors. Using transgenic Arabidopsis plants in Col-0 eds1-2 pad4-1 background conditionally expressing PAD4 and constitutively expressing EDS1 (ED-P4E1), an EDS1/PAD4 immune response can be triggered by estradiol treatment and can induce expression of defense-related genes and lead to enhanced basal resistance. In order to capture primary transcriptional changes in response to EDS1/PAD4, we performed RNA-seq gene expression analysis in ED-P4E1 plants after estradiol or mock treatment at three time points: 6, 12 and 24 h.
2016-09-27 | GSE80585 | GEO