 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 02, 2014 |
| Title |
Antidiabetic Rosiglitazone Remodels the Adipocyte Transcriptome by Redistributing Transcription to PPARg-Driven Enhancers [Affymetrix] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for PPARg, the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to the NR on DNA, explains positive regulation of gene expression, but ligand-dependent repression is not well understood. We have now addressed this issue by studying the direct effects of rosiglitazone on gene transcription, using global run-on sequencing (GRO-seq). Rosi-induced changes in gene body transcription were pronounced after 10 minutes and correlated with steady-state mRNA levels as well as with transcription at nearby enhancers (eRNAs). Upregulated eRNAs occurred almost exclusively at PPARg binding sites, to which rosi treatment recruited the coactivator MED1. By contrast, transcriptional repression by rosi involved a loss of MED1 from eRNA sites devoid of PPARg and enriched for other TFs including AP-1 factors and C/EBPs. Thus, rosi activates and represses transcription by fundamentally different mechanisms that could inform the future development of antidiabetic drugs.
|
| |
|
| Overall design |
Mature 3T3-L1 were treated with rosi or DMSO. Steady-state mRNA levels were monitored at various time points after the treatment between 0 minutes and 48 hours using Affymetrix Mouse Gene 1.1 ST Array.
|
| |
|
| Contributor(s) |
Step SE, Lim H, Marinis JM, Prokesch A, Steger DJ, You S, Won K, Lazar MA |
| Citation(s) |
24788520 |
| Submission date |
Apr 10, 2014 |
| Last update date |
Apr 18, 2017 |
| Contact name |
Hee-Woong Lim |
| Organization name |
Cincinnati Children's Hospital Medical Center
|
| Department |
Division of Biomedical Informatics
|
| Street address |
3333 Burnet Ave. MLC 7024
|
| City |
Cincinnati |
| State/province |
Ohio |
| ZIP/Postal code |
45229 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
|
| Samples (27)
|
| GSM1366863 |
Adipocyte+Rosi 30min, replicate 1 |
| GSM1366864 |
Adipocyte+Rosi 30min, replicate 2 |
| GSM1366865 |
Adipocyte+Rosi 30min, replicate 3 |
| GSM1366866 |
Adipocyte+Rosi 1h, replicate 1 |
| GSM1366867 |
Adipocyte+Rosi 1h, replicate 2 |
| GSM1366868 |
Adipocyte+Rosi 1h, replicate 3 |
| GSM1366869 |
Adipocyte+Rosi 2h, replicate 1 |
| GSM1366870 |
Adipocyte+Rosi 2h, replicate 2 |
| GSM1366871 |
Adipocyte+Rosi 2h, replicate 3 |
| GSM1366872 |
Adipocyte+Rosi 6h, replicate 1 |
| GSM1366873 |
Adipocyte+Rosi 6h, replicate 2 |
| GSM1366874 |
Adipocyte+Rosi 6h, replicate 3 |
| GSM1366875 |
Adipocyte+Rosi 12h, replicate 1 |
| GSM1366876 |
Adipocyte+Rosi 12h, replicate 2 |
| GSM1366877 |
Adipocyte+Rosi 12h, replicate 3 |
| GSM1366878 |
Adipocyte+Rosi 24h, replicate 1 |
| GSM1366879 |
Adipocyte+Rosi 24h, replicate 2 |
| GSM1366880 |
Adipocyte+Rosi 24h, replicate 3 |
| GSM1366881 |
Adipocyte+Rosi 36h, replicate 1 |
| GSM1366882 |
Adipocyte+Rosi 36h, replicate 2 |
| GSM1366883 |
Adipocyte+Rosi 36h, replicate 3 |
| GSM1366884 |
Adipocyte+Rosi 48h, replicate 1 |
| GSM1366885 |
Adipocyte+Rosi 48h, replicate 2 |
| GSM1366886 |
Adipocyte+Rosi 48h, replicate 3 |
|
| This SubSeries is part of SuperSeries: |
| GSE56747 |
Antidiabetic Rosiglitazone Remodels the Adipocyte Transcriptome by Redistributing Transcription to PPARg-Driven Enhancers |
|
| Relations |
| BioProject |
PRJNA244430 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56688_RAW.tar |
115.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...