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

ABSTRACT: 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

ORGANISM(S): Mus musculus

PROVIDER: GSE105068 | GEO | 2018/12/19

REPOSITORIES: GEO

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

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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.

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-12-19 | GSE117379 | GEO

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

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Project description:Mouse microglia (BV2 cells) were stimulated with a TLR4 ligand (E. coli LPS, 1 µg/ml) for 4h. The Agilent SurePrint G3 Mouse Gene Expression Microarray (G4852A) was used for the analysis, which provides full coverage of genes and transcripts with the most up-to-date content, including mRNAs and lincRNAs (http://www.chem.agilent.com/store/en_US/Prod-G4852A/G4852A). BV2 cells were grown to 80% confluence for four groups: the siRNA control (Group A, cells treated with a non-specific scrambied siRNA control), the LPS-stimulated (Group B, cells treated with the siRNA control plus LPS stimulation), lincRNA-Cox2 siRNA (Group C, cells treated with an siRNA to lincRNA-Cox2), and lincRNA-Cox2 siRNA/LPS stimulated (Group D, cells treated with the lincNRA-Cox2 siRNA plus LPS stimulation). Cells were treated with the siRNAs for 24h, followed by additional culture for 4h in the presence or absence of LPS (E. coli LPS, 1 µg/ml). Total RNAs were prepared with the RNeasy Mini kit (Qiagen) according to the manufacturer’s instruction (Ambion).

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