Effects of innate immune stimuli on PAF1 knockout cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB52223 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:PAF1 knockout and ncgRNA control cells were treated with multiple innate immune stimuli for 3 hours to mimic various microbial stresses.
2022-04-10 | E-MTAB-11620 | biostudies-arrayexpress
Project description:Transcriptional response by macrophages stimulated with selected cytokines or innate immune stimuli
2016-02-09 | E-MTAB-3255 | biostudies-arrayexpress
Project description:Effects of innate immune stimuli on PAF1 knockout cells
2023-11-07 | E-MTAB-11620 | ExpressionAtlas
Project description:Gene expression in metazoans is regulated by RNA Polymerase II (Pol II) promoter-proximal pausing and its release. Previously, we identified that Pol II-associated factor 1 (PAF1) modulates the release of paused Pol II into productive elongation. Here, we find that PAF1 occupies transcriptional enhancers and restrains hyperactivation of a subset of these enhancers. Enhancer activation as the result of Paf1 loss releases Pol II from paused promoters of nearby PAF1 target genes. Knockout of PAF1-regulated enhancers attenuates the release of paused Pol II on PAF1 target genes without major interference in the establishment of pausing at their cognate promoters. Thus, a subset of enhancers can primarily modulate gene expression by controlling the release of paused Pol II in a PAF1-dependent manner.
2017-09-01 | GSE97527 | GEO
Project description:To identify the direct targets of the Paf1/RNA polymerase II complex we compared expression profiles of isogenic wild type and paf1 and ctr9 mutant strains. We also created a Tet-regulated form of Paf1 and monitored expression patterns after shut off of Paf1. Samples were isolated at one hour intervals from 1 to 8 hours after shut off. Experiment Overall Design: Transcripts were compared on Affymetrix microarrays using standard protocols.
2007-09-19 | E-GEOD-3200 | biostudies-arrayexpress
Project description:Type 2 inflammation contributes to the pathology of skin diseases such as atopic dermatitis and urticaria. Type 2 innate lymphoid cells are key mediators of skin inflammation by releasing type 2 cytokines in response to certain environmental stimuli. We recently found that Rag1 knockout mice exhibit more pronounced skin inflammation in a mouse model of atopic-dermatitis-like disease, despite lacking adaptive immune cells like T helper 2 cells, implicating a critical role of type 2 innate lymphoid cells in this condition. The goal of this study was to characterize transcriptional differences between WT and Rag KO type 2 innate lymphoid cells to determine if Rag knockout leads to cell-intrinsic alterations in innate lymphoid cell function.
2024-05-04 | GSE202232 | GEO
Project description:The control of promoter-proximal pausing and the release of RNA polymerase II (RNA Pol II) is a widely used mechanism for regulating gene expression in metazoans, especially for genes that respond to environmental and developmental cues. Here, we identify Pol II associated Factor 1 (PAF1) as a major regulator of promoter-proximal pausing. Knockdown of PAF1 leads to increased release of paused Pol II into gene bodies at thousands of genes. Genes with the highest levels of paused Pol II exhibit the largest redistribution of Pol II from the promoter-proximal region into the gene body in the absence of PAF1. PAF1 depletion results in increased nascent transcription and increased levels of phosphorylation of Pol II’s c-terminal domain on serine 2 (Ser2P). These changes can be explained by the recruitment of the Ser2P kinase Super Elongation Complex (SEC) effecting increased release of paused Pol II into productive elongation, thus establishing a novel function for PAF1 as a major regulator of pausing in metazoans. ChIP-seq of Pol II of different forms, SEC subunits, PAFc subunits and H2Bub in human cell lines targeted by PAF1 or scramble shRNA. ChIP-seq of total Pol II in HCT116 cells targeted by BRE1A or scramble shRNA. ChIP-seq of total Pol II in S2 cells targeted by Paf1 or LacZ RNAi. Total RNA-seq, nascent RNA-seq and GRO-seq in HCT116 cells targeted by PAF1 or scramble shRNA.
2015-08-13 | E-GEOD-70408 | biostudies-arrayexpress
Project description:Amyloid precursor protein (APP) and its cleaved products have been reported to have important functions in CNS health, including in memory and synapse formation, cell survival and neuroprotection. Furthermore APP and its cleaved products have been shown to be transiently increased in response to various CNS stressors, suggesting a role in response to acute cellular injury. In an attempt to further understand the function of APP in response to CNS injury, we have used intracranial LPS injection as an inflammatory injury model in APP knock out mice (APPKO). Our data show that innate immune responses to LPS injection is significantly blunted in APPKO mice compared to APP sufficient wild type (BL6) mice. Morphologically, glial cells in APPKO mice appear less reactive, with shorter ramified processes and smaller cell bodies in response to LPS. Additionally, quantitative RT-PCR analysis for several glia markers and innate immune cytokine levels (e.g. TNF?, IL-6, IL-1? and IL-10) showed significantly reduced expression levels in LPS injected APPKO mice. In vitro cell culture assays confirmed this attenuated response to LPS stimulation by primary microglial cells isolated from APPKO mice. Our data suggests that APP full length protein and/or its cleaved products are necessary to mount a complete and effective innate immune cell response to inflammatory injury.
| S-EPMC4598170 | biostudies-literature
Project description:Pleiotropic transcription regulator RNA polymerase II (Pol II)-associated factor 1 (PAF1) governs multiple transcriptional steps and the deposition of several epigenetic marks. However, it remains unclear how ultimate transcriptional outcome is determined by PAF1 and whether it relates to PAF1-controlled epigenetic marks. We utilize rapid degradation systems and reveal direct PAF1 functions in governing pausing partially by recruiting Integrator-PP2A (INTAC), in addition to ensuring elongation. Following acute PAF1 degradation, destabilized polymerase undergoes early termination or effective release, which presumably relies on skewed balance between INTAC and P-TEFb resulting in hyperphosphorylated substrates including SPT5. Impaired Pol II progression during elongation, along with altered pause release frequency, determines the final transcriptional outputs. Moreover, PAF1 degradation causes a cumulative decline in histone modifications. These epigenetic alterations in chromatin likely further influence the production of transcripts from PAF1 target genes.
2022-01-30 | GSE192848 | GEO
Project description:The goal of this study was to characterize altered inducible immune networks in Systemic onset juvenile idiopathic arthritis (sJIA), an IL-1-driven autoinflammatory disease of unknown etiology. To this end, we developed a high-throughput assay that quantifies the transcriptional and protein-level responses of blood leukocytes to innate stimuli. Herein, we report transcriptional data from healthy adult blood stimulated with 16 different conditions, including TLR ligands, cytosolic receptor ligands and inflammatory cytokines. We further report blood transcriptional profiles from sJIA patients with various disease activity and treatment statuses, both ex vivo (baseline) and after in vitro stimulation with a subset of innate stimuli including heat-killed bacterial pathogens.
2017-09-19 | GSE103500 | GEO