The polymorphic PolyQ tail protein of the Mediator Complex, Med15, regulates variable response to stress
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ABSTRACT:
PROVIDER: PRJNA533112 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8910510_1.fastq.gz | Fastqsanger.gz | |||
| SRR8910510_2.fastq.gz | Fastqsanger.gz | |||
| SRR8910520_1.fastq.gz | Fastqsanger.gz | |||
| SRR8910520_2.fastq.gz | Fastqsanger.gz | |||
| SRR8910530_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:The Mediator is composed of multiple of proteins in the head, body, tail and CDK subunits conserved from yeast to humans. However, not all the components are required for transcription. Components of the tail subunit are not essential but to varying degrees are required for changes in transcription to stress. While some stresses are familiar such as heat, desiccation, and starvation, others are exotic yet elicit a physical stress response. MCHM is a hydrotrope that induces growth arrest in yeast. By exploiting genetic variation, specifically in Med15, between yeast strains, we found that Med15 with the polyQ expansion conferred MCHM sensitivity. This sensitivity was not from a loss of function as the reciprocal hemizygous hybrids were all sensitive, suggesting that there is an incompatibility between Mediator complexes from genetic divergent yeast strains. Transcriptomics from yeast expressing the incompatible Med15 changed expression in diverse pathways. Expansion of polyQ tracts in Med15 resulted in multiple isoforms which were mostly from likely post-translational modifications. Stability of Med15 was dependent on Ydj1, a chaperone and the incompatible Med15 allele was expressed at lower levels and less stable than the compatible Med15 allele. Med15 is tethered to the rest of the Mediator complex via Med2 and 3. Deletion of either Med2 or Med3 changes the Med15 isoform patterns in the in a similar manner whereas deletion of Med5, a distal component of the tail did not change the pattern. The med2 and 3 mutants are similarly sensitive to MCHM while med5 mutants are not. Differences between the Med15 alleles extend to responses to different stresses. Whereas the incompatible allele of Med15 improved growth to chemicals that produce free radicals, and the compatible allele of Med15 improved growth to reducing agents, caffeine, and hydroxyurea. This may reflect the positive and negative role that Med15 has in transcription.
2020-04-06 | GSE129898 | GEO
Project description:The yeast Mediator complex can be divided into three modules, designated Head, Middle and Tail. Tail comprises the Med2, Med3, Med5, Med15 and Med16 protein subunits, which are all encoded by genes that are individually non-essential for viability. In cells lacking Med16, Tail is displaced from Head and Middle. However, inactivation of MED5/MED15 and MED15/MED16 are synthetically lethal, indicating that Tail performs essential functions as a separate complex even when it is not bound to Middle and Head. We have used the N-Degron method to create temperature sensitive (ts) mutants in the Mediator tail subunits Med5, Med15 and Med16 to study the immediate effects on global gene expression when each subunit is individually inactivated, and when MED5/15 or MED15/16 are inactivated together.
2013-06-07 | GSE47712 | GEO
Project description:The yeast Mediator complex can be divided into three modules, designated Head, Middle and Tail. Tail comprises the Med2, Med3, Med5, Med15 and Med16 protein subunits, which are all encoded by genes that are individually non-essential for viability. In cells lacking Med16, Tail is displaced from Head and Middle. However, inactivation of MED5/MED15 and MED15/MED16 are synthetically lethal, indicating that Tail performs essential functions as a separate complex even when it is not bound to Middle and Head. We have used the N-Degron method to create temperature sensitive (ts) mutants in the Mediator tail subunits Med5, Med15 and Med16 to study the immediate effects on global gene expression when each subunit is individually inactivated, and when MED5/15 or MED15/16 are inactivated together. All Degron constructs were expressed from their normal chromosomal location under the control of their respective endogenous promoters. We isolated RNA from each strain as early as 45 minutes after changing from the permissive to the restrictive growth conditions to minimize possible secondary effects on gene expression that are not directly caused by the Degron construct(s).
2013-06-07 | E-GEOD-47712 | biostudies-arrayexpress
Project description:The Mediator is composed of multiple subunits conserved from yeast to humans and plays a central role in transcription. The tail components are not required for basal transcription but are required for responses to different stresses. While some stresses are familiar, such as heat, desiccation, and starvation, others are exotic, yet yeast can elicit a successful stress response. 4-Methylcyclohexane methanol (MCHM) is a hydrotrope that induces growth arrest in yeast. We found that a naturally occurring variation in the Med15 allele, a component of the Mediator tail, altered the stress response to many chemicals in addition to MCHM. Med15 contains two polyglutamine repeats (polyQ) of variable lengths that change the gene expression of diverse pathways. The Med15 protein existed in multiple isoforms and its stability was dependent on Ydj1, a protein chaperone. The protein level of Med15 with longer polyQ tracts was lower and turned over faster than the allele with shorter polyQ repeats. MCHM sensitivity via variation of Med15 was regulated by Snf1 in a Myc-tag-dependent manner. Tagging Med15 with Myc altered its function in response to stress. Genetic variation in transcriptional regulators magnified genetic differences in response to environmental changes. These polymorphic control genes were master variators.
| S-EPMC7094212 | biostudies-literature
Project description:Gene expression was compared for wild type yeast (BY4741) and yeast lacking Gal11/Med15 and Med3, or from a gal11-myc med3â strain. The gal11-myc allele shows a partial loss of function when combined with med3â. Expression was analyzed for yeast grown in YPD as well as in CSM. We also examined gene expression of the wild type strain BY4742 grown in YPD and include that data here. Gene expression was compared for wild type yeast (BY4741 and BY4742) and yeast lacking Gal11/Med15 and Med3, or from a gal11-myc med3â strain.
2011-08-31 | E-GEOD-31774 | biostudies-arrayexpress
Project description:Transcriptomics profile of polyQ expressing U2OS cells and clofazimine treated polyQ expressing U2OS cells
| PRJNA923331 | ENA
Project description:To better understand the mechanism by which CFZ impacts polyQ toxicity, we conducted a transcriptomic analysis in polyQ94-EGFP expressing U2OS (5μM, 8 days). Data from a transcriptomics experiment in polyQ94-U2OS cells treated with CFZ (5 μM, 8day) was compared to a DMSO-treated control.
2023-05-11 | GSE222758 | GEO
Project description:Mediator subunits Med17 (Srb4) and Med15 (Gal11) were subjected to ChIP in wild type yeast, med18 (srb5), med20 (srb2), and med2 med3 med15 (triple mutant) yeast, all in kin28-anchor away yeast after 1 hr rapamycin treatment to evict Kin28 from the nucleus. This results in inactivation of Kin28, which reduces Mediator turnover at promoters and allows stronger Mediator ChIP signal at promoters. <br></br>Both Med17 and Med15 were tagged with myc and precipitated using the monoclonal antibody against c-myc. Please note that a specific control for rapamycin treatment was not performed in this experiment, as that has been well documented in the literature for this experiment, using what is called the anchor away method. The untagged sample is a control for non-specific immunoprecipitation.
2017-12-01 | E-MTAB-5824 | biostudies-arrayexpress
Project description:The multiprotein Mediator complex is an important regulator of RNA polymerase II-dependent genes in eukaryotic cell. In contrast to the situation in many other eukaryotes, the conserved Med15 protein is not a stable component of Mediator isolated from fission yeast. We now demonstrate that Med15 exists in a protein complex together with Hrp1, an ATP-dependent chromatin remodeling protein. The Med15/Hrp1 subcomplex is not a component of the core Mediator complex, but can interact with the repressive L-Mediator conformation. Deletion of MED15 and HRP1 cause similar effects on global steady-state levels of mRNA, but only MED15 is required for galactose-dependent activation of the inv1 gene. Hrp1 has been found in complex with other proteins and genome-wide analysis demonstrates that Med15 only associates with a distinct subset of Hrp1-bound gene promoters. Global analysis reveals that Hrp1-binding normally is associated with increased histone H3 density, but at promoters also bound by Med15, histone H3 density is instead increased. Our findings reveal that Med15 functions as a separate entity in fission yeast and indicate that the function and organization of the Mediator complex may differ significantly between eukaryotes. Keywords: ChIP-chip
2010-09-21 | GSE10079 | GEO
Project description:We've demonstrated that plants are resistant to the overexpression of polyglutamine (polyQ) extended proteins that cause protein aggregation and Huntington's disease in human cells. To investigate which proteins, maintain polyQ proteins correctly folded and avoid polyQ aggregates in plant cells. Our goal is to identify therapeutic candidate proteins that can potentially be used to treat Huntington's disease in human cell models.
2023-07-17 | PXD041001 | Pride