Mus musculus
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ABSTRACT:
PROVIDER: PRJNA108129 | ENA |
REPOSITORIES: ENA
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Project description:High- and low-grade inflammatory responses represent a hallmark of numerous pathologies such as sepsis and bacterial infection or insulin resistance and obesity, respectively. Here we describe an unexpected co-activator function of receptor interacting protein (RIP) 140 for nuclear factor (NF) kB, a master transcriptional regulator of inflammation in multiple tissues. Genetic as well as acute deficiency of RIP140, which has been characterized as a co-repressor of various nuclear receptors on metabolic target genes, led to the inhibition of the proinflammatory program in macrophages, mediated by RIP140’s direct impact on cytokine gene promoter activity. Intriguingly, RIP140’s co-activator function in this setting was found to rely on direct protein-protein interactions with the NFκB subunit p65 and histone acetylase CREB-binding protein (CBP). RIP140-dependent control of proinflammatory gene expression via p65/CBP may, therefore, represent a molecular rational for the cellular integration of metabolic and inflammatory pathways. Keywords: expression profiling
2008-03-31 | GSE10386 | GEO
Project description:High- and low-grade inflammatory responses represent a hallmark of numerous pathologies such as sepsis and bacterial infection or insulin resistance and obesity, respectively. Here we describe an unexpected co-activator function of receptor interacting protein (RIP) 140 for nuclear factor (NF) kB, a master transcriptional regulator of inflammation in multiple tissues. Genetic as well as acute deficiency of RIP140, which has been characterized as a co-repressor of various nuclear receptors on metabolic target genes, led to the inhibition of the proinflammatory program in macrophages, mediated by RIP140âs direct impact on cytokine gene promoter activity. Intriguingly, RIP140âs co-activator function in this setting was found to rely on direct protein-protein interactions with the NFκB subunit p65 and histone acetylase CREB-binding protein (CBP). RIP140-dependent control of proinflammatory gene expression via p65/CBP may, therefore, represent a molecular rational for the cellular integration of metabolic and inflammatory pathways. Keywords: expression profiling Gene expression profiling was done for macrophages from RIP140 knockout or wild-type mice. RNA isolation, cDNA and cRNA synthesis, and hybridization to arrays of type Mouse Genome 430 2.0 from Affymetrix (Santa Clara, CA, USA) were performed according to manufacturerâs recommendations. 3 arrays per genotype were hybridized. Microarray data were analysed based on ANOVA using a commercial software package (Micro Array Solution, version 1.0, SAS Institute, Cary, NC, USA). Standard settings were used, except the following specifications: log-linear mixed models were fitted for values of perfect-matches, with genotype considered to be constant and the array-id random. Custom CDF with Unigene based gene/transcript definitions was used to annotate the arrays.
2010-05-22 | E-GEOD-10386 | biostudies-arrayexpress
Project description:To map gene regulation downstream of cholesterol overload and NF-kappaB signaling in smooth muscle cells (SMCs), we cultured primary aortic SMCs from wildtype mice with cyclodextrin-complexed cholesterol or the prototypical NF-kappaB activator, tumor necrosis factor (TNF), or both.
2023-05-29 | E-MTAB-12069 | biostudies-arrayexpress
Project description:Given the intimate link between inflammation and dysregulated cell proliferation in cancer we investigated cytokine-triggered gene expression in different cell cycle stages. High density microarray analysis revealed that G1 release primes and cooperates with the cytokine-driven gene response. This effect is transmitted through CDK6 which shares the ability to regulate expression of inflammatory genes with its functional homologue CDK4. CDK6 contributes to the regulation of inflammatory gene expression by physical and functional cooperation with the NF-κB subunit p65 in the nucleus. ChIPSeq experiments showed a tight co-recruitment of CDK6 and p65 to enhancers and promoters of many transcriptionally active NF-κB target genes. While CDK6 recruitment to distinct chromatin regions of inflammatory target genes had no effect on histone modifications, it was essential for proper loading of NF-κB p65 to its cognate binding sites and for the function of p65 coactivators such as TRIP6. Furthermore, cytokine-inducible nuclear translocation and chromatin association of CDK6 depends on the kinase activity of TAK1 and p38. These results have widespread biological implications, as aberrant CDK6 expression or activation that is frequently observed in human tumors cooperates with NF-κB to shape the cytokine- and chemokine-repertoire in chronic inflammation and cancer. Four sets of experiments were performed in total (Exp1-4). Within each of these sets biological duplicates (Rep1-2) were included and analyzed. HeLa control cells or cells with established shRNA-mediated knockdown of CDK4 or CDK6 were analyzed. Cells were subjected to cell cycle arrest or were released from the arrested state for 6h. Cells were treated for 30 minutes with Interleukin-1-alpha at the arrested state or after release or were left untreated.
2013-12-31 | E-GEOD-52465 | biostudies-arrayexpress
Project description:Given the intimate link between inflammation and dysregulated cell proliferation in cancer we investigated cytokine-triggered gene expression in different cell cycle stages. High density microarray analysis revealed that G1 release primes and cooperates with the cytokine-driven gene response. This effect is transmitted through CDK6 which shares the ability to regulate expression of inflammatory genes with its functional homologue CDK4. CDK6 contributes to the regulation of inflammatory gene expression by physical and functional cooperation with the NF-κB subunit p65 in the nucleus. ChIPSeq experiments showed a tight co-recruitment of CDK6 and p65 to enhancers and promoters of many transcriptionally active NF-κB target genes. While CDK6 recruitment to distinct chromatin regions of inflammatory target genes had no effect on histone modifications, it was essential for proper loading of NF-κB p65 to its cognate binding sites and for the function of p65 coactivators such as TRIP6. Furthermore, cytokine-inducible nuclear translocation and chromatin association of CDK6 depends on the kinase activity of TAK1 and p38. These results have widespread biological implications, as aberrant CDK6 expression or activation that is frequently observed in human tumors cooperates with NF-κB to shape the cytokine- and chemokine-repertoire in chronic inflammation and cancer.
2013-12-31 | GSE52465 | GEO
Project description:Given the intimate link between inflammation and dysregulated cell proliferation in cancer we investigated cytokine-triggered gene expression in different cell cycle stages. Transcriptome analysis revealed that G1 release through CDK6 and CDK4 primes and cooperates with the cytokine-driven gene response. CDK6 physically and functionally interacts with the NF-?B subunit p65 in the nucleus and is found at enhancers and promoters of many transcriptionally active NF-?B target genes. CDK6 recruitment to distinct chromatin regions of inflammatory genes was essential for proper loading of p65 to its cognate binding sites and for the function of p65 coactivators such as TRIP6. Furthermore, cytokine-inducible nuclear translocation and chromatin association of CDK6 depends on the kinase activity of TAK1 and p38. These results have widespread biological implications, as aberrant CDK6 expression or activation that is frequently observed in human tumors cooperates with NF-?B to shape the cytokine- and chemokine-repertoire in chronic inflammation and cancer. 10 samples, five different antibodies for ChIP, no replicates, unstimulated cells as controls
2013-12-31 | E-GEOD-52469 | biostudies-arrayexpress
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
2014-05-01 | GSE54089 | GEO
Project description:Acetylation of p65 at lysine 314 is important for late NF-k(kappa)B-dependent gene expression
| PRJNA116417 | ENA
Project description:Given the intimate link between inflammation and dysregulated cell proliferation in cancer we investigated cytokine-triggered gene expression in different cell cycle stages. Transcriptome analysis revealed that G1 release through CDK6 and CDK4 primes and cooperates with the cytokine-driven gene response. CDK6 physically and functionally interacts with the NF-κB subunit p65 in the nucleus and is found at enhancers and promoters of many transcriptionally active NF-κB target genes. CDK6 recruitment to distinct chromatin regions of inflammatory genes was essential for proper loading of p65 to its cognate binding sites and for the function of p65 coactivators such as TRIP6. Furthermore, cytokine-inducible nuclear translocation and chromatin association of CDK6 depends on the kinase activity of TAK1 and p38. These results have widespread biological implications, as aberrant CDK6 expression or activation that is frequently observed in human tumors cooperates with NF-κB to shape the cytokine- and chemokine-repertoire in chronic inflammation and cancer.
2013-12-31 | GSE52469 | GEO
Project description:Increasing evidence shows that many transcription factors execute important biologic functions independent from their DNA-binding capacity. The NF-κB p65 (RELA) subunit is a central regulator of innate immunity. Here, we investigated the relative functional contribution of p65 DNA-binding and dimerization in p65-deficient human and murine cells reconstituted with single amino acid mutants preventing either DNA-binding (p65 E/I) or dimerization (p65 FL/DD). DNA-binding of p65 was required for RelB-dependent stabilization of the NF-κB p100 protein. The antiapoptotic function of p65 and expression of the majority of TNF-α–induced genes were dependent on p65’s ability to bind DNA and to dimerize. Chromatin immunoprecipitation with massively parallel DNA sequencing experiments revealed that impaired DNA-binding and dimerization strongly diminish the chromatin association of p65. However, there were also p65-independent TNF-α–inducible genes and a subgroup of p65 binding sites still allowed some residual chromatin association of the mutants. These sites were enriched in activator protein 1 (AP-1) binding motifs and showed increased chromatin accessibility and basal transcription. This suggests a mechanism of assisted p65 chromatin association that can be in part facilitated by chromatin priming and cooperativity with other transcription factors such as AP-1.
2018-12-08 | GSE116284 | GEO