Drosophila melanogaster
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA227455 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Expression profiling following depletion of Mediator Cdk8 module subunits Cdk8, Cyclin C (CycC), Med12 and Med13 72 hours after dsRNA treatment of Drosophila melanogaster S2 cells. Results provide insight into the role of individual Cdk8 module subunits in regulation of transcription. 22 samples. 2 Cdk8 dsRNA, 4 CycC dsRNA, 4 Med12 dsRNA, 4 Med13 dsRNA, 8 control samples including 4 Luciferase (Luc) dsRNA and 4 GFP dsRNA
2014-04-29 | E-GEOD-52343 | biostudies-arrayexpress
Project description:Expression profiling following depletion of Mediator Cdk8 module subunits Cdk8, Cyclin C (CycC), Med12 and Med13 72 hours after dsRNA treatment of Drosophila melanogaster S2 cells. Results provide insight into the role of individual Cdk8 module subunits in regulation of transcription.
2014-04-29 | GSE52343 | GEO
Project description:The Mediator complex plays a pivotal role in facilitating RNA polymerase II-dependent transcription in eukaryotes. Within this complex, the CDK8 kinase module (CKM), comprising CDK8, Cyclin C (CycC), Med12, and Med13, serves as a dissociable subcomplex that modulates the activity of the small Mediator complex. Genetic studies in Drosophila have revealed distinct phenotypes associated with mutations in CKM subunits, yet the underlying mechanism has remained unknown. Using Drosophila as a model, we generated transgenic strains to individually or simultaneously deplete the four CKM subunits in all possible combinations, uncovering unique phenotypes in the eyes and wings. Depletion of CDK8-CycC enhanced E2F1 target gene expression and promoted cell-cycle progression, whereas Med12-Med13 depletion had no significant impact on these processes. Conversely, depleting Med12-Med13 altered the expression of ribosomal protein genes and fibrillarin, reduced nascent protein synthesis, indicating a severe reduction in ribosome biogenesis and cellular growth compared to the loss of CDK8-CycC. These findings reveal distinct in vivo roles for CKM subunits, with Med12-Med13 disruption having a more pronounced effect on ribosome biogenesis and protein synthesis .
2024-11-20 | GSE275182 | GEO
Project description:Gene expression profile in CDK8 and Cyclin C homozygous mutants (the third instar larvae) is determined using Affymetrix GeneChip Drosophila Genome 2.0 Array
2012-06-01 | E-MTAB-1066 | biostudies-arrayexpress
Project description:The Mediator kinase module regulates eukaryotic transcription by phosphorylating transcription-related targets and by modulating the association of Mediator and RNA Polymerase II. The activity of its catalytic core, cyclin-dependent kinase 8 (CDK8), is controlled by Cyclin C and MED12, with its deregulation contributing to numerous malignancies. Here, we combine in vitro biochemistry, crosslinking coupled to mass spectrometry and in vivo studies to describe the binding location of the N-terminal segment of MED12 on the CDK8/Cyclin C complex and to gain mechanistic insights into the activation of CDK8 by MED12. Our data demonstrate that the N-terminal portion of MED12 wraps around CDK8, whereby it positions an "activation helix" close to the T-loop of CDK8 for its activation. Intriguingly, mutations in the activation helix that are frequently found in cancers do not diminish the affinity of MED12 for CDK8, yet likely alter the exact positioning of the activation helix. Furthermore, we find the transcriptome-wide gene expression changes in human cells that result from a mutation in the MED12 activation helix to correlate with deregulated genes in breast and colon cancer. Last, functional assays in presence of kinase inhibitors reveal that binding of MED12 remodels the active site of CDK8 and thereby precludes the inhibition of ternary CDK8 complexes by type-II kinase inhibitors. Taken together, our results not only allow us to propose a revised model of how CDK8 activity is regulated by MED12, but they also offer a path forward in developing small molecules that target CDK8 in its MED12-bound form.
2020-01-04 | GSE135458 | GEO
Project description:Mediator is regarded a general co-activator of RNA-Polymerase II dependent transcription but not much is known about its function and regulation in mouse pluripotent embryonic stem cells (mESC). One means of controlling Mediator function is provided by binding of the Cdk8 module (Med12, Cdk8, Ccnc and Med13) to Mediator. Here we report that the Cdk8 module subunit Med12 operates together with PRC1 to silence developmental key genes in the pluripotent state. At the molecular level, PRC1 is required to assemble ncRNA containing Med12-Mediator complexes at promoters of repressed genes. In the course of cellular differentiation the H2A-ubiquitin binding protein Zrf1 abrogates PRC1-Med12 binding and facilitates the recruitment of Cdk8 into Mediator. Remodeling of the Mediator-associated protein complex converts Mediator into a transcriptional enhancer that mediates ncRNA-dependent activation of Polycomb target genes
2016-05-24 | GSE73352 | GEO
Project description:RNA sequencing of HCT116 colon cancer cells following single and combined depletions of Mediator kinase module subunits CDK8, CDK19, MED12, MED13 and MED13L and the BET family protein BRD4. The results provide insight into the shared and specific functions of kinase module subunits and BRD4 in regulation of expression of transcriptional programs including genes associated with cancer acquired super-enhancers.
2018-04-02 | E-MTAB-5873 | biostudies-arrayexpress
Project description:Temporal coordination of developmental programs is necessary for normal ontogeny, but the mechanism by which this is accomplished is poorly understood. We have previously shown that two components of the Mediator CDK8 module, CENTER CITY (CCT/MED12) and GRAND CENTRAL (GCT/MED13), are required for timing of pattern formation during embryogenesis in Arabidopsis. Here, we performed global gene expression analyses of wild-type, cct-1, and gct-2 seedlings (above-ground portions only) to help analyze their post-embryonic phenotypes. Our results suggest that MED12 and MED13 act as global regulators of developmental timing by fine-tuning expression of temporal regulatory genes.
2014-09-22 | GSE56155 | GEO
Project description:Temporal coordination of developmental programs is necessary for normal ontogeny, but the mechanism by which this is accomplished is poorly understood. We have previously shown that two components of the Mediator CDK8 module, CENTER CITY (CCT/MED12) and GRAND CENTRAL (GCT/MED13), are required for timing of pattern formation during embryogenesis in Arabidopsis. Here, we performed global gene expression analyses of wild-type, cct-1, and gct-2 seedlings (above-ground portions only) to help analyze their post-embryonic phenotypes. Our results suggest that MED12 and MED13 act as global regulators of developmental timing by fine-tuning expression of temporal regulatory genes. Seeds of wild-type Col-0, cct-1, and gct-2 were sown in Fafard #2 soil. Seedlings (above-ground portions only) were harvested when the first two leaf primordia were 1 mm in length, which was at day 7 for wild-type seedlings and day 9 for the two mutants. 75-100 seedlings were used for each of three biological replicates.
2014-09-22 | E-GEOD-56155 | biostudies-arrayexpress
Project description:Chemical cross-linking coupled to mass spectrometry was used to study binary and ternary complexes involving cyclin-dependent kinase 19 (CDK19), cyclin-C, and an N-terminal fragment of subunit 12 of the Mediator complex (MED12 1-100). Cross-linking was performed using disuccinimidyl suberate (DSS). These results were generated in the context of the study published as Klatt et al., A precisely positioned MED12 activation helix stimulates CDK8 kinase activity, Proc. Natl. Acad. Sci. USA 2020 (DOI: 10.1073/pnas.1917635117) with the associated data set PXD015394, but were not included in the article.
2020-05-18 | PXD019251 | Pride