Identification of genes regulated by the phosphotylation of PPARgamma
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE22033 | GEO | 2010/05/28
SECONDARY ACCESSION(S): PRJNA128891
REPOSITORIES: GEO
Similar Datasets
Project description:In order to identify the molecular mechanisms of PPARgamma phosphorylation at Set273, we generated cell-lines of PPARgamma KO MEFs expressing wtPPARgamma or S273APPARgamma. In addition, because our data showed that PPARgamma ligand drugs such as rosiglitazone and MRL24 blocked this phopshorylation, we treated cells with these drugs, then prepared RNA samples to look at the gene profiling. PPARgamma KO MEFs were introduced by wtPPARgamma or S273APPARgamma. Cells were differentiated for 6 days. Then, wtPPARgamma-introduced KO MEFs were treated with either 1 uM rosiglitazone or 1uM MRL24 for 24h. Cells were harvested and we purified total RNA samples.
2010-06-08 | E-GEOD-22033 | biostudies-arrayexpress
Project description:The nuclear receptor Peroxisome Proliferator Activated Receptor gamma (PPARgamma) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that macrophage respiration is enhanced by rosiglitazone, an activating PPARgamma ligand, in a PPARgamma dependent manner. Moreover, PPARgamma is required for macrophage respiration even in the absence of exogenous ligand. Unexpectedly, the absence of PPARgamma dramatically affects the oxidation of glutamine. Both glutamine and PPARgamma have been implicated in alternative activation (AA) of macrophages and PPARgamma was required for IL4-dependent gene expression and stimulation of macrophage respiration. Remarkably, depletion of PPARgamma phenocopied the effects of glutamine depletion on transcription. Thus, PPARgamma supports alternative activation by facilitating glutamine metabolism. Yet PPARgamma expression is itself markedly increased by IL4. Thus, PPARgamma functions at the center of a feed forward loop that is central to AA of macrophages.
2018-09-06 | GSE111103 | GEO
Project description:The nuclear receptor Peroxisome Proliferator Activated Receptor gamma (PPARgamma) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that macrophage respiration is enhanced by rosiglitazone, an activating PPARgamma ligand, in a PPARgamma dependent manner. Moreover, PPARgamma is required for macrophage respiration even in the absence of exogenous ligand. Unexpectedly, the absence of PPARgamma dramatically affects the oxidation of glutamine. Both glutamine and PPARgamma have been implicated in alternative activation (AA) of macrophages and PPARgamma was required for IL4-dependent gene expression and stimulation of macrophage respiration. Remarkably, depletion of PPARgamma phenocopied the effects of glutamine depletion on transcription. Thus, PPARgamma supports alternative activation by facilitating glutamine metabolism. Yet PPARgamma expression is itself markedly increased by IL4. Thus, PPARgamma functions at the center of a feed forward loop that is central to AA of macrophages.
2018-09-06 | GSE111104 | GEO
Project description:The nuclear receptor Peroxisome Proliferator Activated Receptor gamma (PPARgamma) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that macrophage respiration is enhanced by rosiglitazone, an activating PPARgamma ligand, in a PPARgamma dependent manner. Moreover, PPARgamma is required for macrophage respiration even in the absence of exogenous ligand. Unexpectedly, the absence of PPARgamma dramatically affects the oxidation of glutamine. Both glutamine and PPARgamma have been implicated in alternative activation (AA) of macrophages and PPARgamma was required for IL4-dependent gene expression and stimulation of macrophage respiration. Remarkably, depletion of PPARgamma phenocopied the effects of glutamine depletion on transcription. Thus, PPARgamma supports alternative activation by facilitating glutamine metabolism. Yet PPARgamma expression is itself markedly increased by IL4. Thus, PPARgamma functions at the center of a feed forward loop that is central to AA of macrophages.
2018-09-06 | GSE111102 | GEO
Project description:Energy-storing white adipocytes maintain their identity by suppressing the gene program defining energy-burning thermogenic brown/beige adipocytes. Here, we reveal that the protein-protein interaction between the transcriptional co-regulator ZFP423 and brown/beige cell determination factor, EBF2, is essential for restraining the thermogenic phenotype of white adipose tissue (WAT). Disruption of the ZFP423-EBF2 protein interaction through CRISPR-Cas9 gene editing triggers widespread “browning” of WAT in adult mice. Mechanistically, adipocyte Zfp423 deficiency induces an EBF2 NuRD-to-BAF co-regulator switch and a shift in PPARgamma occupancy to thermogenic genes. This shift in PPARgamma occupancy increases the anti-diabetic efficacy of the PPARgamma agonist rosiglitazone in obesity while diminishing the unwanted weight-gaining effect of the drug. These data indicate that ZFP423 controls EBF2 co-activator recruitment and PPARgamma occupancy to determine the thermogenic plasticity of adipocytes and raise the concept of targeting transcriptional brakes in adipocyte gene expression as a therapeutic strategy to induce thermogenic adipocyte biogenesis in obesity.
2022-05-01 | GSE175654 | GEO
Project description:Energy-storing white adipocytes maintain their identity by suppressing the gene program defining energy-burning thermogenic brown/beige adipocytes. Here, we reveal that the protein-protein interaction between the transcriptional co-regulator ZFP423 and brown/beige cell determination factor, EBF2, is essential for restraining the thermogenic phenotype of white adipose tissue (WAT). Disruption of the ZFP423-EBF2 protein interaction through CRISPR-Cas9 gene editing triggers widespread “browning” of WAT in adult mice. Mechanistically, adipocyte Zfp423 deficiency induces an EBF2 NuRD-to-BAF co-regulator switch and a shift in PPARgamma occupancy to thermogenic genes. This shift in PPARgamma occupancy increases the anti-diabetic efficacy of the PPARgamma agonist rosiglitazone in obesity while diminishing the unwanted weight-gaining effect of the drug. These data indicate that ZFP423 controls EBF2 co-activator recruitment and PPARgamma occupancy to determine the thermogenic plasticity of adipocytes and raise the concept of targeting transcriptional brakes in adipocyte gene expression as a therapeutic strategy to induce thermogenic adipocyte biogenesis in obesity.
2022-05-01 | GSE175653 | GEO
Project description:PPARγ is a member of the nuclear receptor family for which agonist ligands have anti-growth effects. However, clinical studies using PPARγ ligands as a monotherapy failed to show a beneficial effect. Here we have studied the effects of PPARγ activation with chemotherapeutic agents in current use for specific cancers. We observed a striking synergy between rosiglitazone and platinum-based drugs in several different cancers both in vitro and using transplantable and chemically induced âspontaneousâ tumor models. The effect appears to be due in part to PPARγ-mediated downregulation of metallothioneins, proteins that have been shown to be involved in resistance to platinum-based therapy. These data strongly suggest combining PPARγ agonists and platinum-based drugs for the treatment of certain human cancers Experiment Overall Design: Cells were treated with either DMSO/control, rosiglitazone, carboplatin or combination or rosiglitazone and carboplatin in duplicate for 24 hr. RNA was isolated and microarray analysis carried out by the Dana-Farber Cancer Institute Microarray Core.
2009-04-30 | E-GEOD-7035 | biostudies-arrayexpress
Project description:Histone acetyltransferases (HATs) GCN5/PCAF and CBP/p300 are transcription coactivators. However, how these HATs regulate ligand-induced nuclear receptor target gene expression remains unclear. Here we show in mouse embryonic fibroblasts (MEFs), deletion of GCN5/PCAF specifically eliminates acetylation on H3K9 (H3K9Ac) while deletion of CBP/p300 selectively reduces acetylation on H3K18 and H3K27 (H3K18/27Ac). Treating MEFs with a specific ligand for nuclear receptor PPARdelta induces sequential increases of H3K18/27Ac and H3K9Ac on the promoter of PPARdelta target gene Angptl4, which correlates with a robust ligand-induced Angptl4 expression. Inhibiting transcription elongation blocks ligand-induced H3K9Ac but not H3K18/27Ac on Angptl4 promoter. Finally, we show CBP/p300 and their HAT activities are required, while GCN5/PCAF and H3K9Ac are dispensable, for ligand-induced PPARdelta target gene expression in MEFs. These results highlight the substrate and site specificities of HATs in cells, and suggest that GCN5/PCAF- and CBP/p300-mediated histone acetylations play distinct roles in regulating ligand-induced nuclear receptor target gene expression. PCAF and GCN5 have some redundant function. To identify PCAF/GCN5-regulated genes, immortalized MEFs with PCAF knockout and GCN5 conditional knockout were infected with retroviruses expressing either Cre recombinase or vector alone. We prepared duplicated RNAs from either vector or Cre infected cells (PCAF-/-;GCN5+/- or PCAF-/-;GCN5+/-) and RNAs from either Vector or Cre infected the other independently immortalized cells for 6 affymetrix microarray.
2013-12-31 | E-GEOD-20008 | biostudies-arrayexpress
Project description:In this study we sought to determine if the knockout of hepatocyte PPARgamma expression alter transcriptomics of the livers of mice with diet-induced NASH, and if there was a hepatocyte-specific PPARgamma dependent regulation of gene expression in TZD treated mice. Specifically, adult PPARg floxed male mice were fed a high fat, cholesterol and fructose (HFCF) diet for 24 weeks. After this period of time, half of the mice were injected with AAV8-TBG-Cre to knockout PPARgamma in hepatocytes (KO mice). The other half of the mice were injected with AAV8-TBG-Null, and served as controls (C mice). A subset of PPARg floxed mice were fed a low fat, cholesterol and fructose (LFCF) diet, and they were injected with AAV8-TBG-Null to generate LFCF-controls. Two weeks after AAV8 injections, half of the HFCF-fed mice in each group (C and KO) were switched to a HFCF diet containing rosiglitazone maleate (TZD, 50mg/kg of diet) for eight additional weeks. Mice were kept in their respective diets for 8 additional weeks too. At the end of the study, the livers were collected to assess hepatic gene expression with RNA-seq (performed by Novogen, Inc.)
2021-01-15 | GSE162276 | GEO
Project description:Transcriptional analysis of PPARgamma activation in control and PPARgamma null macrophages
| PRJNA435934 | ENA