Transcriptional and chromatin regulation in interferon and innate antiviral gene expression

Au-Yeung, Nancy; Horvath, Curt M.

doi:10.1016/j.cytogfr.2018.10.003

Cited by 51 publications

(40 citation statements)

References 76 publications

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“…We observed an enrichment of sequence motifs within these clusters for transcription factors controlling endoderm cell fate (FOXA, HNF1), lung cell fate (NKX), AT2 cell fate (CEBP) and AT2 cell signaling (ETS) ( Maeda et al, 2007 ; Morrisey et al, 2013 ; Morrisey and Hogan, 2010 ). Further supporting immune regulation of AT2 cell gene expression, we observed an enrichment of motifs for factors involved in immune signaling such as STAT, IRF, and FOS/JUN ( Au-Yeung and Horvath, 2018 ; Mogensen, 2018 ; Figure 3G , Supplementary file 6 ).…”

Section: Resultsmentioning

confidence: 55%

Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes

Wang

Chiou

Poirion

et al. 2020

eLife

160

173

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Respiratory failure associated with COVID-19 has placed focus on the lungs. Here, we present single-nucleus accessible chromatin profiles of 90,980 nuclei and matched single-nucleus transcriptomes of 46,500 nuclei in non-diseased lungs from donors of ~30 weeks gestation,~3 years and ~30 years. We mapped candidate cis-regulatory elements (cCREs) and linked them to putative target genes. We identified distal cCREs with age-increased activity linked to SARS-CoV-2 host entry gene TMPRSS2 in alveolar type 2 cells, which had immune regulatory signatures and harbored variants associated with respiratory traits. At the 3p21.31 COVID-19 risk locus, a candidate variant overlapped a distal cCRE linked to SLC6A20, a gene expressed in alveolar cells and with known functional association with the SARS-CoV-2 receptor ACE2. Our findings provide insight into regulatory logic underlying genes implicated in COVID-19 in individual lung cell types across age. More broadly, these datasets will facilitate interpretation of risk loci for lung diseases.

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Section: Resultsmentioning

confidence: 55%

Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes

Wang

Chiou

Poirion

et al. 2020

eLife

160

173

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“…Extracellular secreted type I IFNs (IFN-α/IFN-β) play the first battle against viral infection. Actually, type I IFNs, secreted from infected cells, bind to their transmembrane receptors activating STAT1 and STAT2 and trigger IFN-stimulated gene (ISG) expression which rapidly generates a cellular antiviral state [ 55 ]. Whereas, type II IFN-γ is an important mediator of immunity and inflammation, since it plays a crucial role in macrophage activation, autoimmunity and Th1 response.…”

Section: Egcg Molecular Mechanisms That Could Counteract Covid-19 mentioning

confidence: 99%

Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?

Menegazzi

Campagnari

Bertoldi

et al. 2020

IJMS

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Some coronavirus disease 2019 (COVID-19) patients develop acute pneumonia which can result in a cytokine storm syndrome in response to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. The most effective anti-inflammatory drugs employed so far in severe COVID-19 belong to the cytokine-directed biological agents, widely used in the management of many autoimmune diseases. In this paper we analyze the efficacy of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea leaves and a well-known antioxidant, in counteracting autoimmune diseases, which are dominated by a massive cytokines production. Indeed, many studies registered that EGCG inhibits signal transducer and activator of transcription (STAT)1/3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factors, whose activities are crucial in a multiplicity of downstream pro-inflammatory signaling pathways. Importantly, the safety of EGCG/green tea extract supplementation is well documented in many clinical trials, as discussed in this review. Since EGCG can restore the natural immunological homeostasis in many different autoimmune diseases, we propose here a supplementation therapy with EGCG in COVID-19 patients. Besides some antiviral and anti-sepsis actions, the major EGCG benefits lie in its anti-fibrotic effect and in the ability to simultaneously downregulate expression and signaling of many inflammatory mediators. In conclusion, EGCG can be considered a potential safe natural supplement to counteract hyper-inflammation growing in COVID-19.

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“…ISGF3 translocates to the nucleus where STAT1 is further phosphorylated for full activation. Within the nucleus, ISGF3 binds to IFN-stimulated response elements present in the promoters of IFN-stimulated genes (ISGs), which then effect an antiviral cellular environment [for a comprehensive review on IFN signaling, see ( 1 )].…”

Section: Introductionmentioning

confidence: 99%

“…However, ISG expression is more nuanced in reality. A subset of ISGs are direct targets of IRF3/7 and can be induced with or without downstream IFN signaling ( Figure 1 ) ( 1 ). Other ISGs are both basally expressed and IFN-inducible, while still others are cell-type specific ( 19 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

All About the RNA: Interferon-Stimulated Genes That Interfere With Viral RNA Processes

Yang

2020

Front. Immunol.

113

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Interferon (IFN) signaling induces the expression of a wide array of genes, collectively referred to as IFN-stimulated genes (ISGs) that generally function to inhibit viral replication. RNA viruses are frequently targeted by ISGs through recognition of viral replicative intermediates and molecular features associated with viral genomes, or the lack of molecular features associated with host mRNAs. The ISGs reviewed here primarily inhibit viral replication in an RNA-centric manner, working to sense, degrade, or repress expression of viral RNA. This review focuses on dissecting how these ISGs exhibit multiple antiviral mechanisms, often through use of varied co-factors, highlighting the complexity of the type I IFN response. Specifically, these ISGs can mediate antiviral effects through viral RNA degradation, viral translation inhibition, or both. While the OAS/RNase L pathway globally degrades RNA and arrests translation, ISG20 and ZAP employ targeted RNA degradation and translation inhibition to block viral replication. Meanwhile, SHFL targets translation by inhibiting -1 ribosomal frameshifting, which is required by many RNA viruses. Finally, a number of E3 ligases inhibit viral transcription, an attractive antiviral target during the lifecycle of negative-sense RNA viruses which must transcribe their genome prior to translation. Through this review, we aim to provide an updated perspective on how these ISGs work together to form a complex network of antiviral arsenals targeting viral RNA processes.

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Transcriptional and chromatin regulation in interferon and innate antiviral gene expression

Cited by 51 publications

References 76 publications

Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes

Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes

Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?

All About the RNA: Interferon-Stimulated Genes That Interfere With Viral RNA Processes

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