The Mediator Subunit MED20 Organizes the Early Adipogenic Complex to Promote Development of Adipose Tissues and Diet-Induced Obesity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA685543 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13257821_1.fastq.gz | Fastqsanger.gz | |||
| SRR13257821_2.fastq.gz | Fastqsanger.gz | |||
| SRR13257822_1.fastq.gz | Fastqsanger.gz | |||
| SRR13257822_2.fastq.gz | Fastqsanger.gz | |||
| SRR13257823_1.fastq.gz | Fastqsanger.gz |
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Project description:MED20 is a non-essential subunit of the transcriptional coactivator Mediator complex, but its physiological function remains largely unknown. Here we show that MED20 plays a key role in the development of adipose tissue and diet-induced obesity. Through affinity purification and candidate screening, we demonstrate that MED20 is targeted for degradation by the anti-obesity CRL4-WDTC1 E3 complex. Depleting MED20 in either 3T3-L1 cells or primary preadipocytes inhibits adipogenesis. Mice with MED20 knocked out in preadipocytes show dramatic defect in the development of brown adipose tissue. Furthermore, removing one allele of Med20 in preadipocytes protects mice from diet-induced obesity, and reverses weight gain in Cul4a- or Cul4b-depleted mice. Mechanistically, MED20 plays a key role in organizing the early adipogenic complex by bridging C/EBPβ and RNA polymerase II and thereby stimulating the transcription of PPARγ. Our study has thus identified MED20 as a potential target for obesity treatment.
2023-12-15 | GSE163281 | GEO
Project description:Transcriptional repression of ribosomal components and tRNAs is coordinately regulated in response to a wide variety of environmental stresses. Part of this response involves the convergence of different nutritional and stress signaling pathways on Maf1, a protein that is essential for repressing transcription by RNA polymerase (pol) III in Saccharomyces cerevisiae. Here we identify the functions buffering yeast cells that are unable to down-regulate transcription by RNA pol III. MAF1 genetic interactions identified in screens of non-essential gene-deletions and conditionally-expressed essential genes reveal a highly interconnected network of 64 genes involved in ribosome biogenesis, RNA pol II transcription, tRNA modification, ubiquitin-dependent proteolysis and other processes. A survey of non-essential MAF1 synthetic sick/lethal (SSL) genes identified six gene-deletions that are defective in transcriptional repression of ribosomal protein (RP) genes following rapamycin treatment. This subset of MAF1 SSL genes included MED20 which encodes a head module subunit of the RNA pol II Mediator complex. Genetic interactions between MAF1 and subunits in each structural module of Mediator were investigated to examine the functional relationship between these transcriptional regulators. Gene expression profiling identified a prominent and highly selective role for Med20 in the repression of RP gene transcription following treatments with rapamycin, chlorpromazine and tunicamycin and in post-diauxic cells. In addition, attenuated repression of RP genes by rapamycin was observed in a strain deleted for the Mediator tail module subunit Med16. The data suggest that Mediator and Maf1 function in parallel pathways to negatively regulate RP mRNA and tRNA synthesis. Keywords: genetic modification, stress response We generated 12 microarray profiles from fluor-reversed replicates of wild-type and med20? strains with or without treatment with rapamycin and under 5 other conditions that repress ribosomal protein gene transcription. The effect of rapamycin on strains deleted for 3 other Mediator subunits was also assessed relative to wild-type. See Willis et al., (2008) in revision.
2008-06-01 | E-GEOD-11397 | biostudies-arrayexpress
Project description:At Schizosaccharomyces pombe centromeres, non-coding RNAs are transcribed by RNA polymerase II and processed by the RNAi machinery to direct heterochromatin formation. Mediator is a regulator of RNA polymerase II transcription and we here demonstrated that it also controls the levels of centromeric transcripts. Loss of the Mediator subunit Med20 increases transcription of non-coding RNAs and disrupts the centromeric heterochromatin structure. We have used tilling arrays to study the gene expression changes in Med20 deletionVs WT and Med20 dcr1 double mutant Vs Dcr1 mutant in exponentially growing fission yeast cells to detect how the Med20 gene affect centromeric expression.
2012-11-06 | GSE32310 | GEO
Project description:Transcriptional repression of ribosomal components and tRNAs is coordinately regulated in response to a wide variety of environmental stresses. Part of this response involves the convergence of different nutritional and stress signaling pathways on Maf1, a protein that is essential for repressing transcription by RNA polymerase (pol) III in Saccharomyces cerevisiae. Here we identify the functions buffering yeast cells that are unable to down-regulate transcription by RNA pol III. MAF1 genetic interactions identified in screens of non-essential gene-deletions and conditionally-expressed essential genes reveal a highly interconnected network of 64 genes involved in ribosome biogenesis, RNA pol II transcription, tRNA modification, ubiquitin-dependent proteolysis and other processes. A survey of non-essential MAF1 synthetic sick/lethal (SSL) genes identified six gene-deletions that are defective in transcriptional repression of ribosomal protein (RP) genes following rapamycin treatment. This subset of MAF1 SSL genes included MED20 which encodes a head module subunit of the RNA pol II Mediator complex. Genetic interactions between MAF1 and subunits in each structural module of Mediator were investigated to examine the functional relationship between these transcriptional regulators. Gene expression profiling identified a prominent and highly selective role for Med20 in the repression of RP gene transcription following treatments with rapamycin, chlorpromazine and tunicamycin and in post-diauxic cells. In addition, attenuated repression of RP genes by rapamycin was observed in a strain deleted for the Mediator tail module subunit Med16. The data suggest that Mediator and Maf1 function in parallel pathways to negatively regulate RP mRNA and tRNA synthesis. Keywords: genetic modification, stress response
2008-06-01 | GSE11397 | GEO
Project description:Saccharomyces cerevisiae strains carrying mutations of the essential Mediator subunit Med11 as well as strains lacking the non-essential Mediator subunits Med2 and Med20 were compared to the corresponding wild-type strains.
2011-04-19 | E-MEXP-3150 | biostudies-arrayexpress
Project description:At Schizosaccharomyces pombe centromeres, non-coding RNAs are transcribed by RNA polymerase II and processed by the RNAi machinery to direct heterochromatin formation. Mediator is a regulator of RNA polymerase II transcription and we here demonstrated that it also controls the levels of centromeric transcripts. Loss of the Mediator subunit Med20 increases transcription of non-coding RNAs and disrupts the centromeric heterochromatin structure. We have used tilling arrays to study the gene expression changes in Med20 deletionVs WT and Med20 dcr1 double mutant Vs Dcr1 mutant in exponentially growing fission yeast cells to detect how the Med20 gene affect centromeric expression. RNA samples were taken from exponentially growing fission yeast cells and reverse transcribed cDNA from the RNA are hybridized to affymetrix pombe tilling arrays: wild type,med20 mutant, Dcr1 mutants and med20,dcr1 double mutant.
2012-11-06 | E-GEOD-32310 | biostudies-arrayexpress
Project description:Mediator Subunit 30 Directs Myc Oncogenesis
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Project description:Mediator complex is an integrative hub for transcriptional regulation. Here we show that Mediator regulates alternative mRNA processing via its Med23 subunit. Combining tandem affinity purification and mass spectrometry, we identified a number of mRNA processing factors that bind to a soluble recombinant Mediator subunit MED23 but not to several other Mediator components. One of these factors, hnRNP L, specifically interacts with MED23 in vitro and in vivo. Consistently, Mediator partially colocalizes with hnRNP L and the splicing machinery in the cell. Functionally Med23 regulates a subset of hnRNP L-targeted alternative splicing (AS) and alternative cleavage and polyadenylation (APA) events as shown by minigene reporters and exon array analysis. ChIP-seq analysis revealed that Med23 can regulate hnRNP L occupancy at their co-regulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, suggesting a novel mechanism for coupling mRNA processing to transcription. Examination of hnRNP L and H3K36me3 enrichment in sictrl and si23 Hela cells
2012-02-24 | E-GEOD-33887 | biostudies-arrayexpress
Project description:Mediator Subunit 30 Directs Myc Oncogenesis [PRO-seq]
2023-11-08 | GSE217548 | GEO
Project description:Mediator Subunit 30 Directs Myc Oncogenesis [RNA-seq]
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