Transcriptome changes after the transfection of cGAS specific agonist G3-YSD
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA855686 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The cGAS-STING signalling has been well recognized as the major pathway response to self and non-self DNA molecule in cytoplasm. Here, we measured the temporal transcriptome dynamic changes after cGAS-STING signalling activation based on cGAS specific agonist G3-YSD transfection
2022-12-09 | GSE207458 | GEO
Project description:Trichomonas vaginalis G3 strain:G3 Raw sequence reads
| PRJNA290805 | ENA
Project description:The hypothesis tested was that lentiviral driven cGAS expression activates antiviral gene expression. Cells were transduced with lentiviruses expressing cGAS or a control (firefly luciferase). Total RNA was harvested 48 h post-transduction and processed for Illumina BeadArray.
2013-12-01 | E-GEOD-52241 | biostudies-arrayexpress
Project description:We show that Manganese (II) is a potent type I-IFN inducing agonist, stimulating cells into an anti-viral state in the absence of infection. Mechanically, Mn2+ treatment led to a profound cGAS-STING-dependent innate immune activation, conferring cells or mice viral resistance.
2018-10-09 | GSE77216 | GEO
Project description:Lecanicillium sp. G3 strain:G3 Genome sequencing and assembly
| PRJNA1073173 | ENA
Project description:Cytosolic DNA activates cyclic GMP-AMP (cGAMP) synthase (cGAS), an innate immune sensor pivotal in anti-microbial defense, senescence, auto-immunity and cancer. cGAS is considered a sequence-independent DNA sensor with limited access to nuclear DNA because of compartmentalization. However, the nuclear envelope is a dynamic barrier and cGAS is present in the nucleus. Here, we identify determinants of nuclear cGAS localization and activation. We show that nuclear-localized cGAS synthesizes cGAMP and induces innate immune activation of dendritic cells, but cGAMP levels are 200-fold lower than following transfection with exogenous DNA. Using cGAS ChIP-seq and a GFP-cGAS knock-in mouse, we find nuclear cGAS enrichment on centromeric satellite DNA, confirmed by imaging, and to a lesser extent with LINE elements. The non-enzymatic N-terminal domain of cGAS determines nucleo-cytoplasmic localization, enrichment on centromeres and activation of nuclear-localized cGAS. These results reveal a preferential functional association of nuclear cGAS with centromeres.
2019-02-27 | GSE125432 | GEO
Project description:Cytosolic DNA activates cyclic GMP-AMP (cGAMP) synthase (cGAS), an innate immune sensor pivotal in anti-microbial defense, senescence, auto-immunity and cancer. cGAS is considered a sequence-independent DNA sensor with limited access to nuclear DNA because of compartmentalization. However, the nuclear envelope is a dynamic barrier and cGAS is present in the nucleus. Here, we identify determinants of nuclear cGAS localization and activation. We show that nuclear-localized cGAS synthesizes cGAMP and induces innate immune activation of dendritic cells, but cGAMP levels are 200-fold lower than following transfection with exogenous DNA. Using cGAS ChIP-seq and a GFP-cGAS knock-in mouse, we find nuclear cGAS enrichment on centromeric satellite DNA, confirmed by imaging, and to a lesser extent with LINE elements. The non-enzymatic N-terminal domain of cGAS determines nucleo-cytoplasmic localization, enrichment on centromeres and activation of nuclear-localized cGAS. These results reveal a preferential functional association of nuclear cGAS with centromeres.
2019-02-27 | GSE125431 | GEO
Project description:RNA-Seq of wild type and Terc-/- in G3 tail, G3 liver, G3 testis, G3 TTF, G3 ASC, G4 early ESC, G4 late ESC
| PRJNA764681 | ENA
Project description:Chemoresistance challenges the clinical application of most widely used platinum-based cancer chemotherapeutics which canonically function through inducing DNA damage. The DNA sensor cyclic GMP–AMP synthase (cGAS) connects genome instability to type I IFN response which confers vulnerability to platinum treatment. Here, by using a high throughput small-molecule-microarray-based screening of cGAS interacting compounds, we identified brivanib, known as an inhibitor of the vascular endothelial growth factor receptor (VEGFR), as a novel cGAS agonist. Brivanib markedly enhanced platinum-induced STING-TBK1-type I IFN response in tumor cells indispensable of cGAS. Importantly, brivanib synergizes the effect of cisplatin in restricting the growth of xenografted Lewis Lung Cancer (LLC) cells by boosting CD8+ T cell response in a cGAS-dependent manner. Mechanistically, brivanib enhances the DNA binding affinity of cGAS by directly targeting leucine 495 of cGAS. Moreover, leucine 495 of cGAS is essential for brivanib-mediated promoting effect on cisplatin-mediated type I IFN response and inhibition of tumor growth. Clinically, higher expression of cGAS in tumor renders a more favorable response to platinum-based chemotherapeutic regimens and better prognosis in lung cancer patient. Taken together, our findings discover cGAS as an unprecedented target of brivanib and provide a rationale for the combination of brivanib with platinum-based chemotherapeutics in cancer treatment.
2022-12-31 | GSE190016 | GEO
Project description:Upon recognition of aberrantly located DNA, the innate immune sensor cGAS activates STING/IRF-3-driven antiviral responses. Here we characterized the ability of a specific variant of the cGAS-encoding gene MB21D1, rs610913, to alter cGAS-mediated DNA sensing and viral infection. rs610913 is a frequent G>T polymorphism resulting in a P261H exchange in the cGAS protein. Data from the International Collaboration for the Genomics of HIV suggested that rs610913 nominally associates with HIV-1 acquisition in vivo. Molecular modeling of cGAS(P261H) hinted towards the possibility for an additional binding site for a potential cellular co-factor in cGAS dimers. However, cGAS(WT) or cGAS(P261H)-reconstituted THP-1 cGAS KO cells shared steady-state expression of interferon-stimulated genes (ISGs), as opposed to cells expressing the enzymatically inactive cGAS(G212A/S213A). Accordingly, cGAS(WT) and cGAS(P261H) cells were less susceptible to lentiviral transduction and infection with HIV-1, HSV-1, and Chikungunya virus as compared to cGAS KO- or cGAS(G212A/S213A) cells. Upon DNA challenge, innate immune activation appeared to be mildly reduced upon expression of cGAS(P261H) compared to cGAS(WT). Finally, DNA challenge of PBMCs from donors homozygously expressing rs610913 provoked a trend towards a slightly reduced type I IFN response as compared to PBMCs from GG donors. Taken together, the steady-state activity of cGAS maintains a base-line antiviral state rendering cells more refractory to ISG-sensitive viral infections. rs610913 failed to grossly differ phenotypically from the wild-type gene, suggesting that cGAS(P261H) and wild-type cGAS share a similar ability to sense viral infections in vivo.
2022-05-25 | GSE203334 | GEO