Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA137431 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:HDXMS comparison of NFkB (p50(39-350)/RelA(19-321) vs NFkB (p50(39-350)/RelA(19-549)
2022-04-12 | MSV000089247 | MassIVE
Project description:Bcl6 and NFkB cistromes mediate opposing reulation of the innate immune response
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Project description:The specific binding of transcription factors to cognate sequence elements is thought to be critical for the generation of specific gene expression programs. The transcription factors nuclear factor kB (NF-kB) and the interferon (IFN) regulatory factors (IRFs) bind to the kB site and the interferon response element (IRE), respectively, of target genes, and they are activated in macrophages after exposure to pathogens. However, how these factors produce pathogen-specific inflammatory and immune responses remains poorly understood. Combining top-down and bottom-up systems biology approaches, we have identified the NF-kB p50 homodimer (p50:p50) as a regulator of IRF responses. First, unbiased genome-wide expression analysis revealed that p50 repressed a subset of IFN-inducible genes through a previously uncharacterized subclass of guanine-rich IRE (G-IRE) sequences, which was substantiated by biochemical and structural analyses. Second, mathematical modeling predicted that p50:p50 might enforce the stimulus-specificity of composite promoters. Indeed, the production of the antiviral regulator IFN-b was rendered stimulus-specific by the binding of p50:p50 to the G-IRE–containing IFNb enhancer to suppress cytotoxic IFN signaling. Specifically, a deficiency in p50 resulted in the inappropriate production of IFN-b in response to bacterial DNA sensed by Toll-like receptor 9. This role for NF-kB p50 in enforcing the specificity of the cellular response to pathogens by binding to a previously uncharacterized subset of IRE sequences alters our understanding of how the NF-kB and IRF signaling systems cooperate to regulate antimicrobial immunity. [BMDM]: Total RNA extracted from wt, p50-/- or ifnar-/- bone marrow derived macrophages (BMDMs) were subjected to stimulation with LPS, CpG or IFNb [MEF]: Total RNA extracted from wt or p50KO primary mouse embryonic fibroblasts were subjected to stimulation with LPS or IFNb
2011-03-01 | E-GEOD-27112 | biostudies-arrayexpress
Project description:The specific binding of transcription factors to cognate sequence elements is thought to be critical for the generation of specific gene expression programs. The transcription factors nuclear factor kB (NF-kB) and the interferon (IFN) regulatory factors (IRFs) bind to the kB site and the interferon response element (IRE), respectively, of target genes, and they are activated in macrophages after exposure to pathogens. However, how these factors produce pathogen-specific inflammatory and immune responses remains poorly understood. Combining top-down and bottom-up systems biology approaches, we have identified the NF-kB p50 homodimer (p50:p50) as a regulator of IRF responses. First, unbiased genome-wide expression analysis revealed that p50 repressed a subset of IFN-inducible genes through a previously uncharacterized subclass of guanine-rich IRE (G-IRE) sequences, which was substantiated by biochemical and structural analyses. Second, mathematical modeling predicted that p50:p50 might enforce the stimulus-specificity of composite promoters. Indeed, the production of the antiviral regulator IFN-b was rendered stimulus-specific by the binding of p50:p50 to the G-IRE–containing IFNb enhancer to suppress cytotoxic IFN signaling. Specifically, a deficiency in p50 resulted in the inappropriate production of IFN-b in response to bacterial DNA sensed by Toll-like receptor 9. This role for NF-kB p50 in enforcing the specificity of the cellular response to pathogens by binding to a previously uncharacterized subset of IRE sequences alters our understanding of how the NF-kB and IRF signaling systems cooperate to regulate antimicrobial immunity.
2011-03-01 | GSE27112 | GEO
Project description:NF-kB plays a crucial role in immunity to infection. This transcription factor consists in different combinatory homo- and hetero-dimers of the five members of the Rel family. cRel/p50-containing dimers have been involved in the development and function of the immune cells. However, the transcriptional roles of these two subunits still remain poorly explored in innate immune cells. By a multiple approach integrating ex vivo genomic analysis and an in vivo experimental study, we have investigated the consequences of the combined absence of cRel and p50 subunits of NF-kB in the innate response to infection. We have performed gene profiling of cRel-/-p50-/- (DKO) and wild type (WT) peritoneal macrophages stimulated with endotoxin for 2, 6 or 18 hours.
2012-11-21 | E-MEXP-3446 | biostudies-arrayexpress
Project description:NFkB is a family of transcriptional factors that are responsible for inflammatory and immune gene expression. RelA, RelB and cRel are the transactivation domain containing family members. P50 encoded by Nfkb1 is the primary dimerization partner. Many NFkB deficient mice are embryonic lethal. In order to identify NFkB dependent genes, MEF were isolated from Rela-/-cRel-/-, Rela-/-cRel-/-Nfkb1-/- and Rela-/-Relb-/-cRel-/- embryos at E12.5. They were treated with 100ng/ml LPS for 1hr and then profiled gene expression by microarray.
2016-06-27 | E-MTAB-4412 | biostudies-arrayexpress
Project description:ATF3 is a central regulator of interferon-beta and interferon-stimulated genes during the innate immune response
| PRJNA260167 | ENA
Project description:OCA-B, OCA-T1, and OCA-T2 belong to a family of transcriptional coactivators that bind to POU transcription factors (TFs) to regulate gene expression in immune cells. Here, we identify IkBz (encoded by the NFKBIZ gene) as the fourth member of the OCA protein family. While originally discovered as an inducible regulator of NFkB, we show here that IkBz shares a microhomology with OCA proteins and uses this segment to simultaneously bind to POU transcription factors and octamer motif-containing DNA. Our functional reporter assays suggest that IkBz requires its interaction with POU TFs to coactivate immune-related genes. This finding is reinforced by our epigenomic analysis of MYD88 L265P-mutant lymphoma cells, which revealed colocalization of IkBz, the POU transcription factor OCT2, and NFkB:p50 at hundreds of DNA elements harboring octamer and kB motifs. These results suggest that IkBz is a transcriptional coactivator that integrates and amplifies the output of NFkB and POU transcription factors at inducible genes in immune cells.
2024-01-09 | GSE239374 | GEO
Project description:The mass spectrometry data describes the phosphorylation of a transcription factor known as interferon regulatory factor 9 (IRF9), under IFNbeta-induced or non-induced conditions. IRF9 is involved in the transcriptional regulation of hundreds of interferon-stimulated genes as part of the innate immune response.
2022-07-20 | MSV000089924 | MassIVE