Impaired gene expression in ATRX-depleted cells following interferon signaling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE194396 | GEO | 2022/08/03
REPOSITORIES: GEO
Similar Datasets
Project description:We investigated the role of the chromatin remodeling protein ATRX on chromatin accessibility specifically upon IFN-β stimulation utilizing stable ATRX knockdown cells.
2022-08-03 | GSE194395 | GEO
Project description:Impaired gene expression in ATRX-depleted cells following interferon signaling
| PRJNA800422 | ENA
Project description:Alterations in chromatin accessibility in ATRX-depleted cells following interferon signaling
| PRJNA800424 | ENA
Project description:Herpes simplex virus 1 (HSV-1) transcribes its genome in a highly coordinated temporal cascade, utilizing the host RNA polymerase II (Pol II). Repression of transcription precedes the cascade's progression in a process requiring viral immediate early (IE) genes, in a phenomenon termed Transient Immediate Early gene Mediated Repression (TIEMR). Given that components of promyelocytic leukaemia nuclear bodies (PML-NBs) are known to rapidly engage incoming HSV-1 genomes, we investigated their potential role in TIEMR regulation. Using siRNA knockdown of PML-NB constituents (PML, DAXX, and ATRX), we unexpectedly observed that ATRX depletion resulted in a significant reduction in nascent viral transcription on viral IE promoters at 1.5 hours post-infection (hpi). ChIP-Seq analysis indicated ATRX is associated with both highly transcriptionally active and transcriptionally restricted regions, indicating that ATRX has diverse functions in the viral genome. We show here that ATRX association with active transcription on IE genes is correlated to the presence of G-quadruplexes (G4s). Drug stabilization of G4s mimicked the effects of ATRX knockdown, significantly reducing transcription initiation on IE genes. These findings suggest that ATRX promotes transcriptional initiation of HSV-1 IE genes by preventing G4 formation. In sum, our results reveal a previously unrecognized pro-transcriptional role for ATRX early in HSV-1 infection.
2025-08-26 | GSE293673 | GEO
Project description:Herpes simplex virus 1 (HSV-1) transcribes its genome in a highly coordinated temporal cascade, utilizing the host RNA polymerase II (Pol II). Repression of transcription precedes the cascade's progression in a process requiring viral immediate early (IE) genes, in a phenomenon termed Transient Immediate Early gene Mediated Repression (TIEMR). Given that components of promyelocytic leukaemia nuclear bodies (PML-NBs) are known to rapidly engage incoming HSV-1 genomes, we investigated their potential role in TIEMR regulation. Using siRNA knockdown of PML-NB constituents (PML, DAXX, and ATRX), we unexpectedly observed that ATRX depletion resulted in a significant reduction in nascent viral transcription on viral IE promoters at 1.5 hours post-infection (hpi). ChIP-Seq analysis indicated ATRX is associated with both highly transcriptionally active and transcriptionally restricted regions, indicating that ATRX has diverse functions in the viral genome. We show here that ATRX association with active transcription on IE genes is correlated to the presence of G-quadruplexes (G4s). Drug stabilization of G4s mimicked the effects of ATRX knockdown, significantly reducing transcription initiation on IE genes. These findings suggest that ATRX promotes transcriptional initiation of HSV-1 IE genes by preventing G4 formation. In sum, our results reveal a previously unrecognized pro-transcriptional role for ATRX early in HSV-1 infection.
2025-08-26 | GSE293672 | GEO
Project description:The cornerstone of mammalian intrinsic and innate immune defense against pathogens is the production of interferons (IFN), cytokines that stimulate anti-pathogen signaling pathways through the simultaneous expression of hundreds of interferon-stimulated genes (ISG). We compared the effects of IFN classes on the cellular proteome and relative restriction of virus progeny production across multiple physiologically relevant cell types and viruses. We integrated global proteome analyses with targeted mass spectrometry (MS), thermal proximity coaggregation-MS (TPCA-MS), and molecular virology assays to determine how ISGs differentially contribute to host antiviral capacities between immune-modulatory cell types. In differentiated macrophage-like monocytic cells, we classified sets of both shared and distinct ISG proteins responsive to each IFN class. We orthogonally confirmed the relative protein alterations using parallel reaction monitoring (PRM) by developing a proteotypic peptide library for ISG markers induced by each IFN class. Additional comparison to stimulation with pro-inflammatory LPS helped to contextualize the observed IFN signatures. We further assessed ISG protein interactions upon IFN types I and II stimulation, observing maintenance of key ISG protein complexes across treatments. Subsequent comparison of macrophage-like monocytic cells to primary keratinocytes enabled us to identify relative ISG abundances, cytokine induction, and antiviral capacities of both cell types across infections with several ubiquitous human viruses. Infections with herpes simplex virus-1 (HSV-1), adenovirus (AdV), and human cytomegalovirus (HCMV) revealed cell type-dependent differences in virus progeny production.
2024-02-28 | PXD046976 | Pride
Project description:The goal of this experiment is to determine the effect of ATRX depletion on telomeric chromatin compaction. We adapted the ATAC-seq to quantify telomere chromatin accessibility. By scoring the ratio of sequence reads that contained 3 - 12 tandem telomeric repeats over the total number of reads in wild-type and ATRX deplted cells, our analysis revealed that CRISPR/Cas9-mediated ATRX depletion induces a progressive telomere de-compaction.
2019-08-26 | GSE130640 | GEO
Project description:In anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and systemic lupus erythematosus (SLE), glomerulonephritis is a severe kidney complication driven by immune cells, including T cells. However, the mechanisms underlying T cell activation in these contexts remain elusive. Here we report that in patients with AAV and SLE, type I interferon (IFN-I) induces T cell differentiation into interferon-stimulated genes-expressing T (ISG-T) cells, which are characterized by an elevated IFN-I signature, an immature phenotype, and cytotoxicity in inflamed tissue. Mechanistically, IFN-I stimulates the expression of interferon regulatory factor 7 (IRF7) in T cells, which in turn induces granzyme B production. In mice, blocking IFN-I signaling reduces IRF7 and granzyme B expression in T cells, thus ameliorating glomerulonephritis. In parallel, spatial transcriptomic analyses of kidney biopsies from patients with AAV or SLE reveal an elevated ISG signature and the presence of ISG-T cells in close proximity to plasmacytoid dendritic cells, the primary producers of IFN-I. Our results from both patients and animal models thus suggest that IFN-I production in inflamed tissue may drive ISG-T cell differentiation to expand the pool of cytotoxic T cells in autoimmune diseases.
2025-05-05 | GSE296304 | GEO
Project description:Heterochromatin in the eukaryotic genome is rigorously controlled by the concerted action of protein factors and RNAs. Here, we investigate the RNA binding function of ATRX, a chromatin remodeler with roles in silencing of repetitive regions of the genome and in recruitment of the polycomb repressive complex 2 (PRC2). We identify ATRX RNA binding regions (RBRs) and discover that the major ATRX RBR lies within the N-terminal region of the protein, distinct from its PHD and helicase domains. Deletion of this ATRX RBR (ATRXRBR) compromises ATRX interactions with RNAs in vitro and in vivo and alters its chromatin binding properties. Genome-wide studies reveal that loss of RNA interactions results in a redistribution of ATRX on chromatin. Finally, our studies identify a role for ATRX-RNA interactions in regulating PRC2 localization to a subset of polycomb target genes.
2020-03-09 | PXD017806 | Pride
Project description:Herpes simplex virus 1 (HSV-1) transcribes its genome in a highly coordinated temporal cascade, utilizing the host RNA polymerase II (Pol II). Repression of transcription precedes the cascade's progression in a process requiring viral immediate early (IE) genes, in a phenomenon termed Transient Immediate Early gene Mediated Repression (TIEMR). Given that components of promyelocytic leukaemia nuclear bodies (PML-NBs) are known to rapidly engage incoming HSV-1 genomes, we investigated their potential role in TIEMR regulation. Using siRNA knockdown of PML-NB constituents (PML, DAXX, and ATRX), we unexpectedly observed that ATRX depletion resulted in a significant reduction in nascent viral transcription on viral IE promoters at 1.5 hours post-infection (hpi). ChIP-Seq analysis indicated ATRX is associated with both highly transcriptionally active and transcriptionally restricted regions, indicating that ATRX has diverse functions in the viral genome. We show here that ATRX association with active transcription on IE genes is correlated to the presence of G-quadruplexes (G4s). Drug stabilization of G4s mimicked the effects of ATRX knockdown, significantly reducing transcription initiation on IE genes. These findings suggest that ATRX promotes transcriptional initiation of HSV-1 IE genes by preventing G4 formation. In sum, our results reveal a previously unrecognized pro-transcriptional role for ATRX early in HSV-1 infection.
2025-08-26 | GSE293675 | GEO