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The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST [WT and SP140 KO RNA-seq]

ABSTRACT: The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST [WT and SP140 KO RNA-seq]

PROVIDER: PRJNA1123735 | ENA |

REPOSITORIES: ENA

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The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST

Project description:Negative regulation of the antiviral cytokine IFN-I is critical to prevent host pathology, but is not fully understood. The highly conserved but understudied epigenetic reader and nuclear body protein SP140 represses IFN-I by an unknown mechanism. We describe the mechanism by which SP140 negatively regulates IFN-I, and include CUT&RUN data in this dataset. We performed anti-HA CUT&RUN on SP140KO macrophages transduced with HA-tagged or untagged SP140. We found that SP140 represses the expression of a novel positive regulator of IFN-I previously annotated as an annexin II receptor, which we rename RESIST (REgulated Stimulator of IFN-I via Stabilization of Transcript). RESIST promotes IFN-I mRNA stability by binding the CCR4-NOT mRNA deadenylase complex and blocking recruitment of the TTP family of RNA-binding proteins, which negatively regulate IFN-I mRNA stability, to CCR4-NOT. Mechanistically, RESIST uses N and C-terminal alpha-helices respectively to either dock to the CCR4-NOT complex or block TTP family binding. We also find SP140 does not bind the Ifnb1 gene itself. Consistent with previous results, SP140 binds genes involved in embryonic development. Our work reveals a new regulator of IFN-I and a new mechanism regulating IFN-I mRNA stability.

2024-08-28 | GSE269315 | GEO

The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST [WT and SP140 KO RNA-seq]

Project description:Negative regulation of the antiviral cytokine IFN-I is critical to prevent host pathology, but is not fully understood. The highly conserved but understudied epigenetic reader and nuclear body protein SP140 represses IFN-I by an unknown mechanism. We describe the mechanism by which SP140 negatively regulates IFN-I, and include RNA-seq data of WT (B6) and SP140 KO BMMs untreated or treated with 100 ug/mL DMXAA for 8 hours in this dataset. We found that SP140 represses the expression of a novel positive regulator of IFN-I previously annotated as an annexin II receptor, which we rename RESIST (REgulated Stimulator of IFN-I via Stabilization of Transcript). RESIST promotes IFN-I mRNA stability by binding the CCR4-NOT mRNA deadenylase complex and blocking recruitment of the TTP family of RNA-binding proteins, which negatively regulate IFN-I mRNA stability, to CCR4-NOT. Mechanistically, RESIST uses N and C-terminal alpha-helices respectively to either dock to the CCR4-NOT complex or block TTP family binding. Our work reveals a new regulator of IFN-I and a new mechanism regulating IFN-I mRNA stability.

2024-08-28 | GSE269808 | GEO

The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST [RNA-seq]

Project description:Negative regulation of the antiviral cytokine IFN-I is critical to prevent host pathology, but is not fully understood. The highly conserved but understudied epigenetic reader and nuclear body protein SP140 represses IFN-I by an unknown mechanism. We describe the mechanism by which SP140 negatively regulates IFN-I, and include RNA-seq of IFNAR KO and SP140 KO IFNAR KO BMMs untreated or treated with 10 ug/mL DMXAA for 4 hours in this dataset. We found that SP140 represses the expression of a novel positive regulator of IFN-I previously annotated as an annexin II receptor, which we rename RESIST (REgulated Stimulator of IFN-I via Stabilization of Transcript). RESIST promotes IFN-I mRNA stability by binding the CCR4-NOT mRNA deadenylase complex and blocking recruitment of the TTP family of RNA-binding proteins, which negatively regulate IFN-I mRNA stability, to CCR4-NOT. Mechanistically, RESIST uses N and C-terminal alpha-helices respectively to either dock to the CCR4-NOT complex or block TTP family binding. Our work reveals a new regulator of IFN-I and a new mechanism regulating IFN-I mRNA stability.

2024-08-28 | GSE269761 | GEO

The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST [ATAC-seq]

Project description:Negative regulation of the antiviral cytokine IFN-I is critical to prevent host pathology, but is not fully understood. The highly conserved but understudied epigenetic reader and nuclear body protein SP140 represses IFN-I by an unknown mechanism. We describe the mechanism by which SP140 negatively regulates IFN-I, and include ATAC-seq data of WT (B6) and SP140 KO BMMs untreated or treated with 100 ug/mL DMXAA for 8 hours in this dataset. We found that SP140 represses the expression of a novel positive regulator of IFN-I previously annotated as an annexin II receptor, which we rename RESIST (REgulated Stimulator of IFN-I via Stabilization of Transcript). RESIST promotes IFN-I mRNA stability by binding the CCR4-NOT mRNA deadenylase complex and blocking recruitment of the TTP family of RNA-binding proteins, which negatively regulate IFN-I mRNA stability, to CCR4-NOT. Mechanistically, RESIST uses N and C-terminal alpha-helices respectively to either dock to the CCR4-NOT complex or block TTP family binding. Our work reveals a new regulator of IFN-I and a new mechanism regulating IFN-I mRNA stability.

2024-08-28 | GSE269811 | GEO

The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST

Project description:The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST

| PRJNA1121189 | ENA

The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST [ATAC-seq]

Project description:The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST [ATAC-seq]

| PRJNA1123732 | ENA

The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST [RNA-seq]

Project description:The antiviral nuclear body protein SP140 represses Ifnb1 transcript stabilization by the novel regulator RESIST [RNA-seq]

| PRJNA1123644 | ENA

Role of the transcriptional regulator SP140 in resistance to bacterial infection via repression of type I interferons

Project description:Type I interferons (IFNs) are essential for anti-viral immunity, but often impair protective immune responses during bacterial infections. An important question is how type I IFNs are strongly induced during viral infections, and yet are appropriately restrained during bacterial infections. The Super susceptibility to tuberculosis 1 (Sst1) locus in mice confers resistance to diverse bacterial infections. Here we provide evidence that Sp140 is a gene encoded within the Sst1 locus that represses type I IFN transcription during bacterial infections. We generated Sp140–/– mice and find they are susceptible to infection by Legionella pneumophila and Mycobacterium tuberculosis. Susceptibility of Sp140–/– mice to bacterial infection was rescued by crosses to mice lacking the type I IFN receptor (Ifnar–/–). Our results implicate Sp140 as an important repressor of type I IFNs that is essential for resistance to bacterial infections.

2021-02-04 | GSE166114 | GEO

Immune-restricted epigenetic reader SP140 maintains macrophage identity and activation states critical to intestinal homeostasis [array]

Project description:Introduction: SP140 is a bromodomain/plant homeo domain (PHD)-containing reader with immune-restricted expression, and single nucleotide polymorphisms (SNPs) within SP140 associate with Crohn’s disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unknown. Results: Individuals carrying CD-associated SNPs within SP140 had defective SP140 mRNA splicing, diminished SP140 protein, and severely suppressed innate immune signatures that stratified them from other CD patients. Conclusion: SP140 is a critical orchestrator of macrophage identity, and a loss of SP140 due to genetic variation contributes to a molecularly defined subset of CD characterized by suppressed innate immunity.

2017-05-03 | GSE89870 | GEO

Immune-restricted epigenetic reader SP140 maintains macrophage identity and activation states critical to intestinal homeostasis [ATAC-Seq]

2017-05-03 | GSE89177 | GEO