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The chromatin remodeling protein ATRX positively regulates IRF3-dependent type I interferon production and interferon-induced gene expression

ABSTRACT: The chromatin remodeling protein ATRX positively regulates IRF3-dependent type I interferon production and interferon-induced gene expression

PROVIDER: PRJNA800638 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17737122_1.fastq.gz	Fastqsanger.gz
	SRR17737122_2.fastq.gz	Fastqsanger.gz
	SRR17737123_1.fastq.gz	Fastqsanger.gz
	SRR17737123_2.fastq.gz	Fastqsanger.gz
	SRR17737124_1.fastq.gz	Fastqsanger.gz

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The chromatin remodeling protein ATRX positively regulates IRF3-dependent type I interferon production and interferon-induced gene expression.

Project description:The chromatin remodeling protein alpha thalassemia/mental retardation syndrome X-linked (ATRX) is a component of promyelocytic leukemia nuclear bodies (PML-NBs) and thereby mediates intrinsic immunity against several viruses including human cytomegalovirus (HCMV). As a consequence, viruses have evolved different mechanisms to antagonize ATRX, such as displacement from PML-NBs or degradation. Here, we show that depletion of ATRX results in an overall impaired antiviral state by decreasing transcription and subsequent secretion of type I IFNs, which is followed by reduced expression of interferon-stimulated genes (ISGs). ATRX interacts with the transcription factor interferon regulatory factor 3 (IRF3) and associates with the IFN-β promoter to facilitate transcription. Furthermore, whole transcriptome sequencing revealed that ATRX is required for efficient IFN-induced expression of a distinct set of ISGs. Mechanistically, we found that ATRX positively modulates chromatin accessibility specifically upon IFN signaling, thereby affecting promoter regions with recognition motifs for AP-1 family transcription factors. In summary, our study uncovers a novel co-activating function of the chromatin remodeling factor ATRX in innate immunity that regulates chromatin accessibility and subsequent transcription of interferons and ISGs. Consequently, ATRX antagonization by viral proteins and ATRX mutations in tumors represent important strategies to broadly compromise both intrinsic and innate immune responses.

| S-EPMC9387936 | biostudies-literature

The chromatin remodeling protein ATRX positively regulates IRF3-dependent type I interferon production and interferon-induced gene expression

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

2022-08-03 | GSE194429 | GEO

Chromatin remodeler ARID1A binds IRF3 to selectively induce antiviral interferon production in macrophages

Project description:Transcription factor IRF3 is critical for the induction of antiviral type I interferon (IFN-I). The epigenetic regulation of IFN-I production in antiviral innate immunity need to be further identified. Here, we report that epigenetic remodeler ARID1A, a critical component of the mSWI/SNF complex, could bind IRF3 and then was recruited to the Ifn-I promoter by IRF3, thus selectively promoting IFN-I but not TNF-α, IL-6 production in macrophages upon viral infection. Myeloid cell-specific deficiency of Arid1a rendered mice more susceptible to viral infection, accompanied with less IFN-I production. Mechanistically, ARID1A facilitates chromatin accessibility of IRF3 at the Ifn-I promoter by interacting with histone methyltransferase NSD2, which methylates H3K4 and H3K36 of promoter region. Our findings demonstrate the new roles of ARID1A and NSD2 in innate immunity, providing insight to the crosstalks of chromatin remodeling, histone modification and transcription factor in the epigenetic regulation of antiviral innate immunity.

2022-07-01 | GSE176452 | GEO

Irf3 phenotyping

Project description:The interferon regulatory factors IRF3 and IRF7 are key players in the regulation of type I and III IFN genes. In this study, we analyzed the role of IRF3 and IRF7 for the host response to influenza A virus infections in Irf3-/-, Irf7-/- and Irf3-/-Irf7-/- knock-out mice.

2016-11-02 | GSE77600 | GEO

Chromatin remodeler ARID1A binds IRF3 to selectively induce antiviral interferon production in macrophages

Project description:Chromatin remodeler ARID1A binds IRF3 to selectively induce antiviral interferon production in macrophages

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Irf3

Project description:Rattus norvegicus Irf3, interferon regulatory factor 3 [Source:RGD Symbol;Acc:1549774], is differentially expressed in 26 experiment(s);

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Irf3

Project description:Rattus norvegicus Irf3, interferon regulatory factor 3 [Source:RGD Symbol;Acc:1549774], is expressed in 4 baseline experiment(s);

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IRF3

Project description:Sus scrofa IRF3, interferon regulatory factor 3 [Source:VGNC Symbol;Acc:VGNC:89206], is expressed in 2 baseline experiment(s);

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irf3

Project description:Xenopus tropicalis irf3, interferon regulatory factor 3 [Source:Xenbase;Acc:XB-GENE-1013733], is expressed in 1 baseline experiment(s);

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Irf3

Project description:Mus musculus Irf3, interferon regulatory factor 3 [Source:MGI Symbol;Acc:MGI:1859179], is differentially expressed in 79 experiment(s);

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