ArticleInternational journal of molecular sciences2023
ISGF3 and STAT2/IRF9 Control Basal and IFN-Induced Transcription through Genome-Wide Binding of Phosphorylated and Unphosphorylated Complexes to Common ISRE-Containing ISGs.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 20 citations in OpenAlex.
- STAT2-IRF1-ISG15-Associated Temporal Immune Reprogramming in Macrophages during Aspergillus fumigatus Infection.Current microbiology · 2026Article
- Cell-Intrinsic Type I Interferon Signaling as a Pleiotropic Orchestrator of CD4 T Cell Immunity.Biomolecules · 2026Review
- IFIT3 stabilizes STING via USP18 to drive M1 macrophage polarization and early inflammation in acute lung injury.Cellular and molecular life sciences : CMLS · 2026Article
- The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- Blood transcriptomic immune signatures in herpes zoster and postherpetic neuralgia: parallel cohort analyses of IFN-related pathway patterns.Frontiers in cellular and infection microbiology · 2026Article
- Phosphatases in tumor cell immune escape: a perspective based on the camouflage, coercion, cytoprotection.Frontiers in cell and developmental biology · 2026Review
- Human neural stem cell-derived exosomes promote functional recovery in subarachnoid hemorrhage via bdnf/trkb pathway activation and astrocyte modulation.Acta neuropathologica communications · 2025Article
- Article
- The Role and Potential Application of IL-12 in the Immune Regulation of Tuberculosis.International journal of molecular sciences · 2025Review
- Cell-type-specific requirement for TYK2 in murine immune cells under steady state and challenged conditions.Cellular and molecular life sciences : CMLS · 2025Article
- Article
- The strategies and mechanisms of enteroviruses to evade innate immunity and the vaccine progress of enteroviruses.Frontiers in cellular and infection microbiology · 2025Review
- Transcriptional control of interferon-stimulated genes.The Journal of biological chemistry · 2024Review
- Type I Interferonopathy among Non-Elderly Female Patients with Post-Acute Sequelae of COVID-19.Viruses · 2024Article
- Knockdown of DJ-1 Resulted in a Coordinated Activation of the Innate Immune Antiviral Response in HEK293 Cell Line.International journal of molecular sciences · 2024Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In addition to the canonical ISGF3 and non-canonical STAT2/IRF9 complexes, evidence is emerging of the role of their unphosphorylated counterparts in IFN-dependent and -independent ISG transcription. To better understand the relation between ISGF3 and U-ISGF3 and STAT2/IRF9 and U-STAT2/IRF9 in IFN-I-stimulated transcriptional responses, we performed RNA-Seq and ChIP-Seq, in combination with phosphorylation inhibition and antiviral experiments. First, we identified a group of ISRE-containing ISGs that were commonly regulated in IFNα-treated WT and STAT1-KO cells. Thus, in 2fTGH and Huh7.5 WT cells, early and long-term IFNα-inducible transcription and antiviral activity relied on the DNA recruitment of the ISGF3 components STAT1, STAT2 and IRF9 in a phosphorylation- and time-dependent manner. Likewise, in ST2-U3C and Huh-STAT1KO cells lacking STAT1, delayed IFN responses correlated with DNA binding of phosphorylated STAT2/IRF9 but not U-STAT2/IRF9. In addition, comparative experiments in U3C (STAT1-KO) cells overexpressing all the ISGF3 components (ST1-ST2-IRF9-U3C) revealed U-ISGF3 (and possibly U-STAT2/IRF9) chromatin interactions to correlate with phosphorylation-independent ISG transcription and antiviral activity. Together, our data point to the dominant role of the canonical ISGF3 and non-canonical STAT2/IRF9, without a shift to U-ISGF3 or U-STAT2/IRF9, in the regulation of early and prolonged ISG expression and viral protection. At the same time, they suggest the threshold-dependent role of U-ISFG3, and potentially U-STAT2/IRF9, in the regulation of constitutive and possibly long-term IFNα-dependent responses.
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