Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA196174 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Deletion of the NF-κB subunit p65/RelA in the hematopoietic compartment results in gene expression changes in lineage-Flk2-c-kit+Sca-1+ cells from mouse bone marrow.
2013-04-04 | GSE45755 | GEO
Project description:Deletion of the NF-κB subunit p65/RelA in the hematopoietic compartment results in gene expression changes in lineage-Flk2-c-kit+Sca-1+ cells from mouse bone marrow. We analyzed lineage-Flk2-c-kit+Sca-1+ cells from the bone marrow of p65 wild-type or knockout mice using the Affymetrix Mouse Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No technical replicates were performed.
2013-04-04 | E-GEOD-45755 | biostudies-arrayexpress
Project description:Post-translational modification of NF-κB subunits provides a mechanism to differentially regulate their activity in response to the many stimuli that can induce this pathway. However, the physiological significance of these modifications is largely unknown and it remains unclear if these have a critical role in the normal and pathological functions of NF-κB in vivo. Among these, phosphorylation of the RelA(p65) Thr505 residue has been described as an important regulator of NF-κB activity in cell lines but its physiological significance was not known. Therefore, to learn more about the role of this pathway in vivo, we generated a knockin mouse with a RelA T505A mutation. Unlike RelA knockout mice, the RelA T505A mice develop normally but exhibit aberrant hepatocyte proliferation following liver partial hepatectomy or damage resulting from carbon tetrachloride treatment. Consistent with these effects, RelA T505A mice exhibit earlier onset of cancer in the N-nitrosodiethylamine (DEN) model of hepatocellular carcinoma. This data reveals a critical pathway controlling NF-κB function in the liver that acts to suppress tumour-promoting activities of RelA.
2015-11-30 | E-MTAB-3596 | biostudies-arrayexpress
Project description:Cellular response to ionizing radiation involves activation of the p53-dependent pathways and activation of the atypical NF-κB pathway. Mechanisms of the crosstalk between these two transcriptional networks include (co)regulation of common gene targets. Novel genes potentially (co)regulated by p53 and NF-κB were found using high-throughput genomics screening in human osteosarcoma U2-OS cells irradiated with a high dose (4 and 10 Gy). Radiation-induced expression in cells with silenced TP53 or RELA (coding the p65 NF-κB subunit) genes was analyzed by RNA-Seq while radiation-induced binding of p53 and RelA (p65) in putative regulatory regions was analyzed by ChIP-Seq, then selected candidates were validated by qPCR. A subset of radiation-modulated genes whose expression was affected by silencing of both TP53 and RELA, and a subset of radiation-upregulated genes where radiation stimulated binding of both p53 and RelA were identified. Competition for the same transcriptional coactivators of p53 and NF-κB was the most probable mechanism of a frequent antagonistic effect of the TP53 and RELA silencing. However, this mode of regulation was noted for 3 genes where radiation-induced binding of both p53 and RelA was observed, namely IL4I1, SERPINE1, and CDKN1A. This suggested a possibility of a direct antagonistic (co)regulation by both factors: activation by NF-κB and inhibition by p53 of IL4I1, and activation by p53 and inhibition by NF-κB of CDKN1A and SERPINE1. On the other hand, radiation-induced binding of both p53 and RelA was observed in a putative regulatory region of RRAD gene whose expression was downregulated both by TP53 and RELA silencing, which suggested a possibility of direct (co)activation by both factors.
2018-02-19 | GSE110800 | GEO
Project description:Nuclear factor kappa B (NF-κB) is a central regulator of inflammation, infection, and immunity pathways and is often dysregulated in autoimmune diseases, inflammatory disorders, and cancers. However, the mechanisms by which different stimuli, including cellular metabolism, modulate NF-κB activation remain unclear. Here, we report that RelA ( p65), a major component of NF-κB, is S-palmitoylated at cysteine 197 and 206 by directly reacting with palmitoyl-CoA. Autopalmitoylation of p65 promotes its nuclear localization and p65-p50 complex formation, thereby enhancing NF-κB transcriptional activities. Furthermore, p65 palmitoylation upregulates RelB expression and promotes non-canonical NF-κB complex formation, further amplifying pathway activation. We also demonstrate that a high-fat diet could enhance p65 palmitoylation and correlate with an increased cytokine production in mouse tissues. These results reveal that lipid metabolism might directly regulate NF-κB activity and suggest that targeting p65 auto-palmitoylation could be a potential therapeutic strategy for diseases with deregulated NF-κB pathway.
2025-01-17 | GSE286561 | GEO
Project description:The p65/RelA factor of NF-κB plays a pivotal role in coordinating gene expression in response to diverse stimuli, including viral infections. At the chromatin level, p65/RelA governs gene transcription and alternative splicing (AS) through promoter enrichment and genomic exon occupancy, respectively. However, the mechanisms underlying the coordination of these processes remain elusive. In this study, we employed the HTLV-1 Tax viral oncoprotein, a potent activator of NF-κB, to investigate the integrative relationship between 3D chromatin architecture and NF-κB-regulated AS. Our analysis revealed that Tax induces a significant reorganization of the 3D genome, resulting in the formation of multigene complexes that comprise genes co-regulated in transcription and in AS. Notably, we found that the Tax-induced gene-gene contact between the two master genes NFKBIA and RELA is associated with their differential regulation in gene expression and alternative splicing, respectively. Through dCas9-mediated approaches, we demonstrated that NFKBIA-RELA interaction is required for alternative splicing regulation and is caused by an intragenic enrichment of p65/RelA on RELA. Via this mechanism, Tax promotes the expression of the splice isoform RELAE6 that exhibits specific gene transactivation capacity at the protein level. Our findings shed light on new regulatory mechanisms upon HTLV-1 Tax and underscore the crucial role of p65/RelA in coordinated regulation of NF-κB-responsive genes at both transcriptional and alternative splicing levels in the context of the 3D genome.
2024-02-03 | GSE233887 | GEO
Project description:The p65/RelA factor of NF-κB plays a pivotal role in coordinating gene expression in response to diverse stimuli, including viral infections. At the chromatin level, p65/RelA governs gene transcription and alternative splicing (AS) through promoter enrichment and genomic exon occupancy, respectively. However, the mechanisms underlying the coordination of these processes remain elusive. In this study, we employed the HTLV-1 Tax viral oncoprotein, a potent activator of NF-κB, to investigate the integrative relationship between 3D chromatin architecture and NF-κB-regulated AS. Our analysis revealed that Tax induces a significant reorganization of the 3D genome, resulting in the formation of multigene complexes that comprise genes co-regulated in transcription and in AS. Notably, we found that the Tax-induced gene-gene contact between the two master genes NFKBIA and RELA is associated with their differential regulation in gene expression and alternative splicing, respectively. Through dCas9-mediated approaches, we demonstrated that NFKBIA-RELA interaction is required for alternative splicing regulation and is caused by an intragenic enrichment of p65/RelA on RELA. Via this mechanism, Tax promotes the expression of the splice isoform RELAE6 that exhibits specific gene transactivation capacity at the protein level. Our findings shed light on new regulatory mechanisms upon HTLV-1 Tax and underscore the crucial role of p65/RelA in coordinated regulation of NF-κB-responsive genes at both transcriptional and alternative splicing levels in the context of the 3D genome.
2024-02-03 | GSE233888 | GEO
Project description:Metastasis suppressor 1 (MTSS1) is a 755 amino acid protein found in the cell cytoplasm which binds to actin and promotes cytoskeleton organization and is a known suppressor of lung adenocarcinoma metastasis This study demonstrated that preservation of MTSS1 protein expression in lung adenocarcinoma was associated with a 20% 5-year survival advantage in patients. Furthermore, overexpression of MTSS1 was found to reduce metastasis and disease progression in an in-vivo orthotopic lung adenocarcinoma mouse model. Nuclear factor kappa B (NF-kB), an important nuclear transcription factor, has been shown to be constitutively active in lung adenocarcinoma and strongly associated with the development of metastasis. The NF-kB RelA/p65 subunit is involved in NF-kB heterodimer formation and subsequent nuclear translocation leading to activation of NF-kB responsive gene transcription. Phosphorylation and acetylation of p65 are critical post-translational modifications required for NF-kB activation. In this study, we demonstrate that MTSS1 expression leads to decreased NF-κB mediated gene transcription through inhibition of p65 phosphorylation. These findings uncover a novel mechanism through which MTSS1 may regulate lung adenocarcinoma metastasis by impairment of NF-κB regulated gene transcription.
2024-07-07 | GSE179644 | GEO
Project description:Using a mouse model with hepatocyte-specific deletion of transcription factor NF-κB RelA (p65), our group has previously revealed the important role of RelA in inducing the acute phase response, maintaining host defense, and preventing liver injury during sepsis. To goal of this study was determine the influence of RelA on hepatic gene changes that provide liver protection during infection. Mice were generated with functional deletion of NF-kappaB RelA (p56) in hepatocytes using a Cre-LoxP system. Mutant mice expressed Cre-recombinase under the transcriptional control of an albumin promotor and homozygous floxed RelA alleles. Wild type control mice lack the Cre-recombinase. Microarray analysis was performed on liver RNA collected from both genotypes of mice in the absence and presence of pneumococcal bacteremia.
2019-06-07 | GSE126642 | GEO
Project description:Pseudogenes are thought to be inactive gene sequences, but recent evidence of extensive pseudogene transcription raised the question of potential function. Here we discover and characterize the sets of lncRNAs induced by inflammatory signaling via TNFα. TNFα regulates hundreds of lncRNAs, including 54 pseudogene lncRNAs, several of which show exquisitely selective expression in response to specific cytokines and microbial components in a NF-κB-dependent manner. Lethe, a pseudogene lncRNA, is selectively induced by proinflammatory cytokines via NF-κB or glucocorticoid receptor agonist, and functions in negative feedback signaling to NF-κB. Lethe interacts with NF-κB subunit RelA to inhibit RelA DNA binding and target gene activation. Lethe level decreases with organismal age, a physiological state associated with increased NF-κB activity. These findings suggest that expression of pseudogenes lncRNAs are actively regulated and constitute functional regulators of inflammatory signaling. RNA profiles of wild type (WT) MEFs treated with TNF-alpha were generated by deep sequencing using Illumina GAIIx. Examination of H3K4me3 histome modification in MEF.
2013-08-05 | E-GEOD-47494 | biostudies-arrayexpress