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| Status |
Public on Aug 01, 2013 |
| Title |
Acute Genome-Wide Effects of Rosiglitazone on PPARγ Transcriptional Networks in Adipocytes |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Here we report, for the first time, the acute effects of the synthetic PPARγ agonist rosiglitazone on the transcriptional network of PPARγ in adipocytes. Treatment with Rosiglitazone for 1 hour leads to acute transcriptional activation as well as repression of a number of genes as determined by genome-wide RNA polymerase II occupancy. Unlike what has been shown for many other nuclear receptors, agonist treatment does not lead to major changes in the occurrence of PPARγ binding sites. However, rosiglitazone promotes PPARγ occupancy at many preexisting sites, and this is paralleled by increased occupancy of the mediator subunit MED1. The increase in PPARγ and MED1 binding is correlated with an increase in transcription of nearby genes indicating that rosiglitazone, in addition to activating the receptor, also promotes its association with DNA, and that this is causally linked to recruitment of mediator and activation of genes. Notably, both Rosiglitazone-activated and -repressed genes are induced during adipogenesis. However, Rosiglitazone-activated genes are markedly more associated with PPARγ than repressed genes and are highly dependent on PPARγ for expression in adipocytes. By contrast, repressed genes are associated with the other key adipocyte transcription factor CCAAT-Enhancer binding protein (C/EBPα), and their expression is more dependent on C/EBPα. This suggests that the relative occupancies of PPARγ and C/EBPα are critical for whether genes will be induced or repressed by PPARγ agonist.
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| Overall design |
Examination of binding of PPARγ, C/EBPα, RNAPII, CBP and MED1 in mature 3T3-L1 adipocytes treated with 1 μM Rosiglitazone and/or 0.1% DMSO for 1 hour.
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| Contributor(s) |
Haakonsson AK, Madsen MS, Nielsen R, Sandelin A, Mandrup S |
| Citation(s) |
23885096 |
| Submission date |
Jul 31, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Susanne Mandrup |
| E-mail(s) |
s.mandrup@bmb.sdu.dk
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| Phone |
+45 6550 2340
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| Organization name |
University of Southern Denmark
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| Department |
Biochemistry and Molecular Biology
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| Street address |
Campusvej 55
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| City |
Odense M |
| ZIP/Postal code |
5230 |
| Country |
Denmark |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (16)
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| GSM1199128 |
PPARγ ChIP-seq, 3T3-L1 Day7 1h DMSO rep1 |
| GSM1199129 |
PPARγ ChIP-seq, 3T3-L1 Day7 1h Rosi rep1 |
| GSM1199130 |
PPARγ ChIP-seq, 3T3-L1 Day7 1h DMSO rep2 |
| GSM1199131 |
PPARγ ChIP-seq, 3T3-L1 Day7 1h Rosi rep2 |
| GSM1199132 |
MED1 ChIP-seq, 3T3-L1 Day7 1h DMSO |
| GSM1199133 |
MED1 ChIP-seq, 3T3-L1 Day7 1h Rosi |
| GSM1199134 |
C/EBPα ChIP-seq, 3T3-L1 Day7 1h DMSO |
| GSM1199135 |
C/EBPα ChIP-seq, 3T3-L1 Day7 1h Rosi |
| GSM1199136 |
RNAPII ChIP-seq, 3T3-L1 Day7 1h DMSO rep1 |
| GSM1199137 |
RNAPII ChIP-seq, 3T3-L1 Day7 1h Rosi rep1 |
| GSM1199138 |
RNAPII ChIP-seq, 3T3-L1 Day7 1h DMSO rep2 |
| GSM1199139 |
RNAPII ChIP-seq, 3T3-L1 Day7 1h Rosi rep2 |
| GSM1199140 |
CBP ChIP-seq, 3T3-L1 Day7 1h DMSO |
| GSM1199141 |
CBP ChIP-seq, 3T3-L1 Day7 1h Rosi |
| GSM1199142 |
Input, 3T3-L1 Day7 1h DMSO |
| GSM1199143 |
Input, 3T3-L1 Day7 1h Rosi |
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| Relations |
| BioProject |
PRJNA213884 |
| SRA |
SRP028367 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE49423_CEBPa_peaks.txt.gz |
759.5 Kb |
(ftp)(http) |
TXT |
| GSE49423_PPARg_Peaks.txt.gz |
765.1 Kb |
(ftp)(http) |
TXT |
| GSE49423_RAW.tar |
689.5 Mb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
| Raw data are available in SRA |
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