Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA261038 | ENA |
REPOSITORIES: ENA
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Project description:U3A cells stably expressing wild-type STAT1 or STAT1-CC were treated with interferon beta (10U/ml) or control for 24 hours to assess effects of stat1 modifications, interferon, and the interaction on gene expression. Keywords: interferon, STAT1, STAT1-CC, STAT1CC, STAT-1C, antiviral RNA was isolated from stable U3A-STAT1 lines stably expressing wild-type STAT1 or STAT1CC, after 24 hour treatment with interferon beta (10U/ml) or control.
2015-09-01 | E-GEOD-61413 | biostudies-arrayexpress
Project description:Interferon-lambdas (IFNλs) serve as critical mediators of antiviral defense at mucosal surfaces. Beyond their established role in regulating innate immune responses during infection, recent evidence demonstrates that IFNλs are constitutively expressed in pathogen-free environments, termed "basal" IFN expression. While intestinal epithelial cells constitutively express all basal IFNλ subtypes (IFNλ1, IFNλ2, and IFNλ3), their individual contributions to antiviral immunity remain poorly defined. Here, we systematically investigate the distinct roles of IFNλ1 and IFNλ2/3 in regulating intrinsic antiviral immunity using human intestinal epithelial T84 cells. Through genetic depletion of IFNλ1 or IFNλ2/3, we show that basal IFNλ2/3, but not IFNλ1, is essential for restricting replication and spread of diverse viruses, including vesicular stomatitis virus (VSV), mammalian orthoreovirus (MRV), rotavirus (RV), and vaccinia virus (VV). Transcriptomic profiling revealed that IFNλ2/3 selectively controls the basal expression of interferon-stimulated genes (ISGs), including key antiviral effectors and components of the IFN signaling machinery (e.g., STAT1, STAT2, IRF9). Loss of IFNλ2/3 reduced total STAT1 protein levels and blunted responsiveness to exogenous IFNλ, indicating compromised interferon signaling capacity. Furthermore, basal IFNλ2/3 was required for activating paracrine JAK/STAT signaling and ISG induction in neighboring bystander cells, thereby amplifying antiviral protection across the epithelial layer. These findings reveal a functional hierarchy among IFNλ subtypes and establish IFNλ2/3 as the dominant, non-redundant regulators of epithelial immune readiness. Our study provides the first comprehensive analysis of basal IFNλ subtype functions in the gut epithelium and underscores the central role of basal IFNλ2/3 in maintaining mucosal antiviral defense.
2026-01-04 | GSE296527 | GEO
Project description:Signal transduction via the Signal Transducer and Activator of Transcription 1 (STAT1) pathway is indispensable for mediating the intracellular effects of interferon-α (IFN-α), interferon-γ (IFN-γ) and other cytokines in the brain and, thereby, crucial for antiviral and antibacterial responses during potential life-threatening CNS infections. However, the role of STAT1 signaling beyond the known IFN-α and IFN-γ effects in immediate antimicrobial defense is highly context-dependent, and studies in the existing literature using STAT1-targeted mouse models under normal physiological conditions remain scarce. Here, we characterized a STAT1 targeted-disruption mouse model (STAT1-/- mice) in the absence of infectious stimuli by quantitative proteome analysis. Soluble hippocampal protein extracts from five female animals per condition (WT, STAT1-/-) were processed with replicate injection, resulting in two technical replicates per biological replicate and, thus, in a total of 20 LC-MS runs to be compared. We utilized an ion mobility-enhanced version of a data-independent acquisition (DIA) workflow with alternating low and elevated energy (referred to as UDMSE). Label-free protein quantification revealed numerous differentially regulated proteins, many of which classified as products of IFN-regulated genes according to Interferome V2.01 (https://interferome.org/interferome/home.jspx), and/or of STAT1 target genes according to the ENCODE transcription factor targets dataset (https://maayanlab.cloud/Harmonizome/dataset/ENCODE+Transcription+Factor+Targets). By integration of transcriptome and proteome data, we detected significant alterations in hippocampal gene and protein expression profiles implicated in neuroinflammatory processes and neuroprotection.
2025-07-14 | PXD062965 | Pride
Project description:Virus infection induces the production of type I and type II interferons (IFN-I and IFN-II), cytokines that mediate the antiviral response. IFN-I (IFN-a and -b) induces the assembly of ISGF3 (interferon-stimulated gene factor 3), a multimeric transcriptional activation complex comprised of STAT1, STAT2 and IRF9. IFN-II (IFN-g) induces the homodimerization of STAT1 to form the GAF (gamma-activated factor) complex. ISGF3 and GAF bind specifically to distinct regulatory DNA sequences located upstream of IFN-I and II inducible genes, respectively, and activate the expression of distinct set of antiviral genes. The balance between the type I and type II IFN pathways plays a critical role in orchestrating the innate and adaptive immune systems. Here, we show that the phosphorylation of STAT1 by IKKε (IkB-related kinase epsilon) inhibits STAT1 homodimerization, and thus GAF formation, but does not disrupt ISGF3 formation. Therefore, virus and/or IFN-I activation of IKKε suppresses GAF-dependent transcription and promotes ISGF3-dependent transcription. In the absence of IKKε, GAF-dependent transcription is enhanced at the expense of ISGF3-mediated transcription, rendering cells less resistant to infection. We conclude that IKKε plays a critical role in regulating the balance between the IFN-I and IFN-II signaling pathways. ChIP-seq libraries were constructed with an antibody targeting STAT1 from bone marrow macrophages treated with interferon
2011-12-01 | E-GEOD-33913 | biostudies-arrayexpress
Project description:U3A cells stably expressing wild-type STAT1 or STAT1-CC were treated with interferon beta (10U/ml) or control for 24 hours to assess effects of stat1 modifications, interferon, and the interaction on gene expression. Keywords: interferon, STAT1, STAT1-CC, STAT1CC, STAT-1C, antiviral
2015-09-01 | GSE61413 | GEO
Project description:Begitt2014 - STAT1 cooperative DNA binding - double GAS polymer model
The importance of STAT1-cooperative DNA binding in type 1 and type 2 interferon signalling has been studies using experimental and modelling approaches. The authors have developed two ODE models to describe STAT1 binding to short promoter regions of DNA, namely "single GAS polymer model" and "double GAS polymer model" considering binding to single or double GAS sites, respectively. The length of DNA in the single GAS model was three sites and four sites in double GAS model. This model correspond to the "double GAS polymer model".
This model is described in the article:
STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling.
Begitt A, Droescher M, Meyer T, Schmid CD, Baker M, Antunes F, Owen MR, Naumann R, Decker T, Vinkemeier U
Nat Immunol. 2014 Feb;15(2):168-76.
Abstract:
STAT1 is an indispensable component of a heterotrimer (ISGF3) and a STAT1 homodimer (GAF) that function as transcription regulators in type 1 and type 2 interferon signaling, respectively. To investigate the importance of STAT1-cooperative DNA binding, we generated gene-targeted mice expressing cooperativity-deficient STAT1 with alanine substituted for Phe77. Neither ISGF3 nor GAF bound DNA cooperatively in the STAT1F77A mouse strain, but type 1 and type 2 interferon responses were affected differently. Type 2 interferon-mediated transcription and antibacterial immunity essentially disappeared owing to defective promoter recruitment of GAF. In contrast, STAT1 recruitment to ISGF3 binding sites and type 1 interferon-dependent responses, including antiviral protection, remained intact. We conclude that STAT1 cooperativity is essential for its biological activity and underlies the cellular responses to type 2, but not type 1 interferon.
This model is hosted on BioModels Database
and identified
by: BIOMD0000000501
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000501 | BioModels
Project description:Begitt2014 - STAT1 cooperative DNA binding - single GAS polymer model
The importance of STAT1-cooperative DNA binding in type 1 and type 2 interferon signalling has been studies using experimental and modelling approaches. The authors have developed two ODE models to describe STAT1 binding to short promoter regions of DNA, namely "single GAS polymer model" and "double GAS polymer model" considering binding to single or double GAS sites, respectively. The length of DNA in the single GAS model was three sites and four sites in double GAS model. This model correspond to the "single GAS polymer model".
This model is described in the article:
STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling.
Begitt A, Droescher M, Meyer T, Schmid CD, Baker M, Antunes F, Owen MR, Naumann R, Decker T, Vinkemeier U
Nat Immunol. 2014 Feb;15(2):168-76.
Abstract:
STAT1 is an indispensable component of a heterotrimer (ISGF3) and a STAT1 homodimer (GAF) that function as transcription regulators in type 1 and type 2 interferon signaling, respectively. To investigate the importance of STAT1-cooperative DNA binding, we generated gene-targeted mice expressing cooperativity-deficient STAT1 with alanine substituted for Phe77. Neither ISGF3 nor GAF bound DNA cooperatively in the STAT1F77A mouse strain, but type 1 and type 2 interferon responses were affected differently. Type 2 interferon-mediated transcription and antibacterial immunity essentially disappeared owing to defective promoter recruitment of GAF. In contrast, STAT1 recruitment to ISGF3 binding sites and type 1 interferon-dependent responses, including antiviral protection, remained intact. We conclude that STAT1 cooperativity is essential for its biological activity and underlies the cellular responses to type 2, but not type 1 interferon.
This model is hosted on BioModels Database
and identified
by: BIOMD0000000500
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000500 | BioModels
Project description:U3A cells expressing Stat1 were transfected with either wild-type PARP9 and DTX3L, or inactive mutants of PARP9 and DTX3L. Stable lines were assessed for gene expression to identify effects of PARP9/DTX3L overexpression on ISG expression. Keywords: interferon, PARP9, DTX3L, antiviral RNA was isolated from stable U3A-STAT1 lines overexpressing either wild-type or inactive mutants of PARP9 and DTX3L.
2015-09-01 | E-GEOD-61411 | biostudies-arrayexpress
Project description:Deciphering the intricate dynamic events governing type I interferon (IFN) signaling is critical to unravel key regulatory mechanisms in host antiviral defense. Here, we leveraged TurboID-based proximity labeling coupled with affinity purification-mass spectrometry to comprehensively map temporal changes to the proximal human proteomes of all seven canonical type I IFN signaling cascade members following IFN stimulation. This established a network of 108 proteins in close proximity to the core members IFNAR1, IFNAR2, JAK1, TYK2, STAT1, STAT2, and IRF9, and validated several known protein assemblies, while also revealing novel, transient associations between key signaling molecules.
2024-05-28 | PXD045482 | Pride
Project description:Small RNAs play a critical role in host-pathogen interaction. In insects, for instance, small RNA-mediated silencing or RNA interference (RNAi) represents the main antiviral defense system. However, the antiviral role of RNAi has not been clearly proven in higher vertebrates. On the contrary, it is well established that the cell response relies on the recognition of viral RNAs by host pattern recognition receptors (PRR) to trigger the activation of the interferon pathway. Based on this evidence, we wished to contribute to this research field by identifying and characterizing small non-coding RNAs produced in mammalian cells upon RNA virus infection. We focused on Sindbis virus (SINV), the prototypical arbovirus, which by definition, is able to infect both vertebrate hosts and invertebrate vectors and triggers the interferon pathway or RNAi, respectively. Taking advantage of large scale sequencing, we cloned and sequenced small RNAs from both mock and SINV-infected mammalian cells (HEK 293 and VERO). We identified a novel population of viral small RNAs (vsRNAs) that accumulate as 20 to 30 nt species during infection. We assessed that this viral small RNA population is modified in 3'end and derived from the activation of the cellular antiviral endoribonuclease RNaseL. Altogether our results indicate a potential role for the SINV-derived small RNAs in the host defense mechanism.
2013-11-19 | E-GEOD-48831 | biostudies-arrayexpress