Expression data from seedlings of two light grown Arabidopsis thaliana CSN mutants and two wild type ecotypes
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ABSTRACT:
ORGANISM(S): Arabidopsis thaliana
PROVIDER: GSE108376 | GEO | 2020/07/28
REPOSITORIES: GEO
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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:COP9 (constitutive photomorphogenesis mutant 9) signalosome (CSN) is composed of eight subunits (CSN1 through CSN8). It acts as an essential regulator of Cullin-RING-ubiquitin ligases (CRLs), which target critical cellular regulators for degradation via the ubiquitin (Ub) proteasome pathway. The role of CSN in adipose tissue development and function has not yet been studied. We sought to determine the role of CSN8, the smallest subunit of the CSN complex, in adipogenesis, adipose tissue maintenance, and metabolic balance. In this study, we generated mice with adipocyte-specific deletion of CSN8 (Csn8AKO) and confirmed the deletion of CSN8 and the disruption of CSN holo-complex formation and Cullin deneddylation in white and brown adiposes. We performed bulk RNA-Seq and identified significant remodeling of white and brown adipose tissues, characterized by adipocyte cell death and inflammation. Specifically, white and brown adipose tissues lacking CSN8 exhibited marked upregulation of apoptotic and pyroptotic cell death, which was associated with alterations in ubiquitination and proteasome activity. Taken together, our data highlight that CSN8/CSN is crucial for maintaining protein homeostasis in adipose tissue, promoting adipocyte survival, supporting adipose tissue maintenance, and overall metabolic health.
2026-02-18 | GSE314831 | GEO
Project description:The COP9 signalosome (CSN) is a conserved protein complex occurring in all eukaryotes. The mammalian CSN consists of eight subunits (CSN1 – CSN8) and possesses an intrinsic metalloprotease JAMM motif localised to CSN5. In addition, it is associated with kinases such as protein kinase CK2 and D and the ubiquitin (Ub) specific protease 15. It regulates cullin-RING Ub ligases (CRLs) that label proteins for proteolysis with poly-Ub chains in the Ub proteasome system (UPS). CRLs contain one of the scaffolding cullins 1 – 7, a RING domain protein e. g. Rbx1, and one of hundreds of substrate binding units such as F-box or BTB proteins that specifically target proteins for ubiquitination. The CSN forms functional supercomplexes with CRLs. It removes the Ub-like protein Nedd8 from cullins by its metalloprotease activity and thereby inactivates CRLs. On the other hand, it is essential for CRL function by protecting components and allowing reassembly of the complexes. As a regulator of the UPS the CSN is involved in cell cycle10, DNA repair and development. Overexpression of CSN subunits has been reported in tumour cells. Up to date nothing is known about CSN biogenesis and its regulation. Ten years ago we have observed that overexpression of selected CSN subunits caused a coordinated increase of all CSN subunits and a de novo biosynthesis of the entire complex. Here we show that overexpression of CSN1 mediates an increase of c-Myc which coordinates CSN subunit expression via microRNAs (miRNAs). miRNAs are evolutionarily conserved, endogenous, small, noncoding RNA molecules of about 22 nucleotides that function as posttranscriptional gene regulators. We found that inhibitors of let-7 family miRNAs or upregulation of c-Myc, which represses let-7 miRNAs, resulted in a coordinated increase of CSN subunits and de novo CSN biogenesis. Keywords: Gene expression analysis of human RNA samples using topic-defined PIQOR™ Ubiquitin-PS Microarrays. Two different platforms were used (these are two different microarray batches which are identical in terms of the spotted cDNAs, but differ in the position of some cDNAs)
2011-10-27 | GSE19085 | GEO
Project description:The COP9 signalosome (CSN) is a conserved protein complex occurring in all eukaryotes. The mammalian CSN consists of eight subunits (CSN1 – CSN8) and possesses an intrinsic metalloprotease JAMM motif localised to CSN5. In addition, it is associated with kinases such as protein kinase CK2 and D and the ubiquitin (Ub) specific protease 15. It regulates cullin-RING Ub ligases (CRLs) that label proteins for proteolysis with poly-Ub chains in the Ub proteasome system (UPS). CRLs contain one of the scaffolding cullins 1 – 7, a RING domain protein e. g. Rbx1, and one of hundreds of substrate binding units such as F-box or BTB proteins that specifically target proteins for ubiquitination. The CSN forms functional supercomplexes with CRLs. It removes the Ub-like protein Nedd8 from cullins by its metalloprotease activity and thereby inactivates CRLs. On the other hand, it is essential for CRL function by protecting components and allowing reassembly of the complexes. As a regulator of the UPS the CSN is involved in cell cycle10, DNA repair and development. Overexpression of CSN subunits has been reported in tumour cells. Up to date nothing is known about CSN biogenesis and its regulation. Ten years ago we have observed that overexpression of selected CSN subunits caused a coordinated increase of all CSN subunits and a de novo biosynthesis of the entire complex. Here we show that overexpression of CSN1 mediates an increase of c-Myc which coordinates CSN subunit expression via microRNAs (miRNAs). miRNAs are evolutionarily conserved, endogenous, small, noncoding RNA molecules of about 22 nucleotides that function as posttranscriptional gene regulators. We found that inhibitors of let-7 family miRNAs or upregulation of c-Myc, which represses let-7 miRNAs, resulted in a coordinated increase of CSN subunits and de novo CSN biogenesis. Keywords: Gene expression analysis of human RNA samples using topic-defined PIQOR™ Ubiquitin-PS Microarrays. Two different platforms were used (these are two different microarray batches which are identical in terms of the spotted cDNAs, but differ in the position of some cDNAs) Gene expression analysis of Hela cells overexpressing either CSN2 or CSN1 was performed to study CSN biogenesis and its regulation. Curcumin, Nr. 8 (Curcumin analogon) and Piceatannol were used for the treatment of Hela cells since they inhibit the CSN associated kinases. The aim was to investigate the effect on the signalosome. For each treatment 50 µM Curcumin, Nr. 8 and Piceatannol were used.
2011-10-26 | E-GEOD-19085 | biostudies-arrayexpress
Project description:The eight-subunit COP9 signalosome (CSN complex), controls the exchange of E3 ubiquitin cullin RING ligase receptors through its deneddylase activity, providing specificity to eukaryotic protein degradation. The conserved eight-subunit CSN complex is required for multicellular development of the filamentous fungus Aspergillus nidulans. The human, as well as the fungal CSN complex assembles through a heptameric subcomplex (pre-CSN complex) that is activated by the integration of the eighth subunit, the catalytic CsnE/5 deneddylase. The focus of this work was to unveil the assembly of the native fungal pre-CSN complex via combined genetic and biochemical approaches. Interactomes of various functional GFP-Csn subunit fusions, produced in pre-CSN deficient fungal double csn subunit gene deletion strains, were compared by affinity purifications coupled to mass spectrometry analyses. With this approach, two distinct heterotrimeric CSN subcomplexes were identified as pre-CSN assembly intermediates, namely CsnA/1-C/3-H/8 and CsnD/4-F/6-G/7 that form independently of CsnB/2 that connects the heterotrimers to a heptameric subcomplex and enables subsequent integration of CsnE/5, yielding in the enzymatically active CSN holocomplex. Surveillance mechanisms control accurate Csn subunit abundances and correct cellular localization for sequential assembly, since deprivation of Csn subunits change the abundance and location of the remaining Csn subunits.
2023-08-10 | PXD043205 | Pride
Project description:The COP9 signalosome (CSN) is a highly conserved eukaryotic protein complex which regulates the Cullin-RING family of ubiquitin ligases and carries out a deneddylase activity that resides in subunit 5 (CSN5). The budding yeast CSN is biochemically active and deletion mutants of each of its subunits exhibit deficiency in deneddylation of cullins, although the biological context of this activity is still unknown in this organism. To further characterize CSN function in budding yeast, we present here a transcriptomic analysis of a S. cerevisiae strain deleted in CSN5/RRI1 gene (hereafter referred to as CSN5), coding for the only canonical subunit of the complex. We show that Csn5 is involved in the modulation of the genes controlling aminoacid and lipid metabolism, and especially ergosterol biosynthesis. These alterations in gene expression correlate with the lower ergosterol levels and increased intracellular zinc content which we observed in csn5 null mutant cells. Two biological replicates, csn5 deleted strain vs. isogenic wild-type strain W303
2013-10-23 | E-GEOD-51563 | biostudies-arrayexpress
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:Salt cress (Eutrema salsugineum, synonymously Thellungiella salsuginea) is an extremophile, a close relative of Arabidopsis. In order to understand the selective mechanisms that shape their complex traits underlying natural variation, we analyzed the physiological and proteomic differences between Shandong (SD) ecotype and Xinjiang (XJ) ecotype.
2022-08-11 | PXD018751 | Pride
Project description:The COP9 signalosome (CSN) is a highly conserved eukaryotic protein complex which regulates the Cullin-RING family of ubiquitin ligases and carries out a deneddylase activity that resides in subunit 5 (CSN5). The budding yeast CSN is biochemically active and deletion mutants of each of its subunits exhibit deficiency in deneddylation of cullins, although the biological context of this activity is still unknown in this organism. To further characterize CSN function in budding yeast, we present here a transcriptomic analysis of a S. cerevisiae strain deleted in CSN5/RRI1 gene (hereafter referred to as CSN5), coding for the only canonical subunit of the complex. We show that Csn5 is involved in the modulation of the genes controlling aminoacid and lipid metabolism, and especially ergosterol biosynthesis. These alterations in gene expression correlate with the lower ergosterol levels and increased intracellular zinc content which we observed in csn5 null mutant cells.
2013-10-23 | GSE51563 | GEO