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Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE117379 | GEO | 2018/12/19

REPOSITORIES: GEO

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Genetic Models Reveal cis and trans Immune-Regulatory Activities for lincRNA-Cox2.

Project description:An inducible gene expression program is a hallmark of the host inflammatory response. Recently, long intergenic non-coding RNAs (lincRNAs) have been shown to regulate the magnitude, duration, and resolution of these responses. Among these is lincRNA-Cox2, a dynamically regulated gene that broadly controls immune gene expression. To evaluate the in vivo functions of this lincRNA, we characterized multiple models of lincRNA-Cox2-deficient mice. LincRNA-Cox2-deficient macrophages and murine tissues had altered expression of inflammatory genes. Transcriptomic studies from various tissues revealed that deletion of the lincRNA-Cox2 locus also strongly impaired the basal and inducible expression of the neighboring gene prostaglandin-endoperoxide synthase (Ptgs2), encoding cyclooxygenase-2, a key enzyme in the prostaglandin biosynthesis pathway. By utilizing different genetic manipulations in vitro and in vivo, we found that lincRNA-Cox2 functions through an enhancer RNA mechanism to regulate Ptgs2. More importantly, lincRNA-Cox2 also functions in trans, independently of Ptgs2, to regulate critical innate immune genes in vivo.

| S-EPMC6291222 | biostudies-literature

Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo (lungs)

Project description:Here we compare gene expression profiles between lungs taken from a Wild type mouse to lungs from a lincRNA-Cox2 knockout mouse The aim of the experiment is to determine what impact lincRNA-Cox2 has on gene expression within the lung

2018-12-19 | GSE105068 | GEO

Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo (macrophages)

Project description:Here we amplified a region in exon 5 of Ptgs2 that contains SNPs to allow us to differenitate between the C57 allele and the MOLF allele

2018-12-19 | GSE117377 | GEO

Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo (lungs and spleens)

Project description:Here we compare gene expression profiles between lungs and spleens following LPS in vivo injection into Wild type, lincRNA-Cox2 knockout and lincRNA-Cox2 mutant mice The aim of the experiment is to determine the cis and trans functions for lincRNA-Cox2 following in vivo LPS challenge within the spleen and lung

2018-12-19 | GSE116354 | GEO

Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo

Project description:Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo

| PRJNA481951 | ENA

Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo (macrophages)

Project description:Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo (macrophages)

| PRJNA481949 | ENA

Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo (lungs)

Project description:Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo (lungs)

| PRJNA414568 | ENA

Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo (lungs and spleens)

Project description:Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2 in vivo (lungs and spleens)

| PRJNA478239 | ENA

Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of human lincRNA genes.

Project description:High-throughput methods based on chromosome conformation capture have greatly advanced our understanding of the three-dimensional (3D) organization of genomes but are limited in resolution by their reliance on restriction enzymes. Here we describe a method called DNase Hi-C for comprehensively mapping global chromatin contacts. DNase Hi-C uses DNase I for chromatin fragmentation, leading to greatly improved efficiency and resolution over that of Hi-C. Coupling this method with DNA-capture technology provides a high-throughput approach for targeted mapping of fine-scale chromatin architecture. We applied targeted DNase Hi-C to characterize the 3D organization of 998 large intergenic noncoding RNA (lincRNA) promoters in two human cell lines. Our results revealed that expression of lincRNAs is tightly controlled by complex mechanisms involving both super-enhancers and the Polycomb repressive complex. Our results provide the first glimpse of the cell type-specific 3D organization of lincRNA genes.

| S-EPMC4281301 | biostudies-literature

lincRNA-Cox2 regulates NLRP3 inflammasome and autophagy mediated neuroinflammation.

Project description:Inflammasome activation plays key roles in host defense, but also contributes to the pathogenesis of auto-inflammatory, and neurodegenerative diseases. As autophagy is connected with both the innate and adaptive immune systems, autophagic dysfunction is also closely related to inflammation, infection, and neurodegeneration. Here we identify that lincRNA-Cox2, previously known as a mediator of both the activation and repression of immune genes expression in innate immune cells, could bind NF-κB p65 and promote its nuclear translocation and transcription, modulating the expression of inflammasome sensor NLRP3 and adaptor ASC. Knockdown of lincRNA-Cox2 inhibited the inflammasome activation and prevented the lincRNA-Cox2-triggered caspase-1 activation, leading to decreased IL-1β secretion and weakened TIR-domain-containing adapter-inducing interferon-β (TRIF) cleavage, thereby enhancing TRIF-mediated autophagy. Elucidation of the link between lincRNA-Cox2 and the inflammasome-autophagy crosstalk in macrophage and microglia reveals a role for lncRNAs in activation of NLRP3 inflammasome and autophagy, and provides new opportunities for therapeutic intervention in neuroinflammation-dependent diseases.

| S-EPMC6294802 | biostudies-other

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