Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA390725 | ENA |
REPOSITORIES: ENA
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Project description:The COP9 signalosome protein complex has a central role in the regulation of development of multi-cellular organisms. While the function of this complex in ubiquitin-mediated protein degradation is well established, results over the past few years have hinted that the COP9 signalosome may function more broadly in the regulation of gene expression. Here, using DamID technology, we show that COP9 signalosome subunit 7 functionally associates with a large number of genomic loci in the Drosophila genome, and show that the expression of many genes within these loci is COP9 signalosome-dependent. This association is likely direct as we show CSN7 binds DNA in vitro. The genes targeted by CSN7 are preferentially enriched for transcriptionally active regions of the genome, and are involved in the regulation of distinct gene ontology groupings including imaginal disc development and cell-cycle control.
2014-09-22 | GSE61605 | GEO
Project description:The COP9 signalosome is a highly conserved multi-protein complex consisting of eight subunits, which influences key developmental pathways through its regulation of protein stability and transcription. In Arabidopsis thaliana, mutations in the COP9 Signalosome exhibit a number of diverse pleiotropic phenotypes. Total or partial loss of COP9 Signalosome function in Arabidopsis leads to misregulation of a number of genes involved in DNA methylation, suggesting that part of the pleiotropic phenotype is due to global effects on DNA methylation. Results: We determined and analyzed the methylomes and transcriptomes of both partial- and total-loss-of-function mutants of the COP9 Signalosome. Our results indicate that the COP9 Signalosome has a global genome-wide effect on methylation and that this effect is at least partially encoded in the DNA. In addition, our analyses suggest that COP9 Signalosome-dependent methylation is related to gene expression regulation in various ways. Differentially methylated regions tend to be closer in the 3D conformation of the genome to differentially expressed genes. These results suggest that the COP9 Signalosome has a more comprehensive effect on gene expression than thought before, and this is partially related to regulation of methylation. The high level of COP9 Signalosome conservation among eukaryotes may also suggest that COP9 Signalosome regulates methylation not only in plants but also in other eukaryotes, including humans. We report the application of Bisulfite-sequencing to compare methylation of two CSN mutants with their corresponding wild types: a non-lethal csn5a-1 mutant, vs. columbia ecotype, and a lethal, csn8 mutant, vs. Wassilewskija ecotype
2020-07-28 | GSE119259 | GEO
Project description:The COP9 signalosome protein complex has a central role in the regulation of development of multi-cellular organisms. While the function of this complex in ubiquitin-mediated protein degradation is well established, results over the past few years have hinted that the COP9 signalosome may function more broadly in the regulation of gene expression. Here, using DamID technology, we show that COP9 signalosome subunit 7 functionally associates with a large number of genomic loci in the Drosophila genome, and show that the expression of many genes within these loci is COP9 signalosome-dependent. This association is likely direct as we show CSN7 binds DNA in vitro. The genes targeted by CSN7 are preferentially enriched for transcriptionally active regions of the genome, and are involved in the regulation of distinct gene ontology groupings including imaginal disc development and cell-cycle control. DamID experiments were done in Drosophila Kc167 cells. Samples were hybridized to 380k NimbleGen arrays with 300 bp probe spacing. The experiment contains 4 samples, three biological replicates and one reverse dye orientation. For each sample Dam-fusion material was hybridized over Dam-only material.
2014-09-22 | E-GEOD-61605 | biostudies-arrayexpress
Project description:Drosophila COP9 Signalosome Subunit 7 interacts with multiple genomic loci
| PRJNA261677 | ENA
Project description:Background: The COP9 signalosome (CSN) consisting of 8 protein subunits (CSN1 through CSN8) is a deneddylase for Cullin-RING ligases (CRLs), essential to the functioning of the ubiquitin-proteasome system. CSN8 is encoded by the Cops8 gene. We have shown that CSN8 plays a key role in the regulation of cardiac protein quality control (PQC), and cardiomyocyte-restricted Cops8 knockout (CSN8-CKO) in perinatal and adult mice causes massive cardiomyocyte necrosis and acute heart failure in mice. Objective: To identify the underlying mechanisms at the transcriptional level, we examined the impact of perinatal CSN8-CKO on myocardial gene expression. Design: Whole mouse genome DNA microarrays (CodeLink) were used to assess myocardial gene expression profiles in Control (CTL), heterozygous (Het-CKO), and homozygous (Hom-CKO) cardiac Cops8 knockout littermate mice at 2- and 3-weeks-of-age. GeneSpring GS software (v.12.5) was used to analyze differentially expressed genes (DEGs). DEGs were analyzed using the GeneGo MetaCore Analytical Suite (http://genego.com; GeneGo, St. Joseph, MI) to identify significantly enriched pathways. Network analysis was performed using R package WGCNA on the expression profiles of DEGs. IPA analysis was also performed. Results: The microarray data revealed 521 DEGs at 3-weeks-of-age with cut-off log2 |fold change|≧1. Among these genes, 271 genes were upregulated and 250 were downregulated. Similarly, at 2-weeks-of-age, out of 78 DEG, 35 genes were upregulated and 43 were downregulated. The transcript levels of many substrate receptors of CRLs (Fbxo14, Fbxo31, Klhdc1, Klhdc7a, Klh31, Klh41) were significantly down-regulated by CSN8-CKO. Consistent with cardiac pathology and prior RNA dot blot analysis results, the microarray analysis revealed significant upregulation of fetal genes (e.g., Nppa, Nppb, Acta1) and down-regulation of many postnatal genes (Actc1, Atp2a2, Pln, Tpm1). Our results suggest that CSN8-CKO-induced decrease in cardiac contractility could be due to decreased transcription of cacna1s, ptgfr and mylk2 genes. Pathways related to cellular stress particularly oxidative stress and vesicular trafficking were also observed to be enriched following CSN8 deficiency in cardiomyocytes. Enrichment of DEGs in chromatin remodeling pathway corroborates the involvement of CSN8 in gene expression regulation. Conclusions: Myocardial gene expression profiles are dynamically affected by CSN8-CKO in mice. Our data strongly suggest that CSN8 is involved in the regulation of myocardial gene expression programs that regulate ubiquitination, chromatin remodeling, and vesicle trafficking in cardiomyocytes.
2017-08-23 | GSE100104 | GEO
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:CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. A genetic modification design type is where an organism(s) has had genetic material removed, rearranged, mutagenized or added, such as knock out. Computed
2010-06-29 | E-GEOD-9204 | biostudies-arrayexpress
Project description:CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. This SuperSeries is composed of the following subset Series: GSE9204: Role of CSN5 in breast cancer (siRNA transfections) GSE9205: Role of CSN5 in breast cancer (array CGH) Refer to individual Series
2010-06-29 | E-GEOD-9206 | biostudies-arrayexpress
Project description:CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. A strain or line experiment design type assays differences between multiple strains, cultivars, serovars, isolates, lines from organisms of a single species. Computed
2010-06-29 | E-GEOD-9205 | biostudies-arrayexpress