Filters
Technology
Platform
GSE54202
Homo sapiens
12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
SUMOylation modulates the transcriptional activity of androgen receptor in a target gene and pathway selective manner.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
Androgen receptor (AR) plays an important regulatory role during prostate cancer development. ARs transcriptional activity is regulated by androgenic ligands, but also by post-translational modifications. To study the role of the AR SUMOylation in genuine chromatin environment, we compared androgen-regulated gene expression and AR chromatin occupancy in PC-3 prostate cancer and HEK293 cell lines stably expressing wild-type (wt) or SUMOylation site-mutated AR (AR-K386R,K520R). Our genome-wide gene expression analyses reveal that the SUMOylation modulates the AR function in a target gene and pathway selective manner. The transcripts that are differentially regulated by androgen and SUMOylation are linked to cellular movement, cell death, cellular proliferation, cellular development and cell cycle. In line with these data, SUMOylation mutant AR cells proliferate faster and are more sensitive to apoptosis. Moreover, ChIP-seq analyses show that the SUMOylation modulates the chromatin occupancy of AR on many loci in a fashion that parallels with their differential androgen-regulated expression. De novo motif analyses show that other transcription factor-binding motifs are differentially enriched at the wtAR- and the AR-K386R,K520R-preferred genomic binding positions. Taken together, our data indicate that SUMOylation does not simply repress the AR activity, but it regulates ARs interaction with the chromatin and the receptors target gene selection.
Publication Title
SUMOylation modulates the transcriptional activity of androgen receptor in a target gene and pathway selective manner.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In addition to the glucocorticoids, the glucocorticoid receptor (GR) is regulated by post-translational modifications, including SUMOylation. We have analyzed how SUMOylation influences the activity of endogenous GR target genes and the receptor chromatin binding by using isogenic HEK293 cells expressing wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR). Gene expression profiling revealed that both dexamethasone up- and down-regulated genes are affected by the GR sumoylation and that the affected genes are significantly associated with pathways of cellular proliferation and survival. The GR3KR-expressing cells proliferated more rapidly and their anti-proliferative response to dexamethasone was less pronounced than in the wtGR-expressing cells. ChIP-seq analyses indicated that the SUMOylation modulates the chromatin occupancy of GR on several loci associated with cellular growth in a fashion which parallels with their differential dexamethasone-regulated expression between the two cell lines. Moreover, genome-wide SUMO-2/3 marks, which were generally associated with active chromatin, showed markedly higher overlap with the wtGR cistrome than with the GR3KR cistrome. In sum, our results indicate that the SUMOylation does not simply repress the GR activity, but regulates the activity of the receptor in a target locus selective fashion, playing an important role in controlling the GR activity on genes influencing cell growth.
Publication Title
SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In addition to the glucocorticoids, the glucocorticoid receptor (GR) is regulated by post-translational modifications, including SUMOylation. We have analyzed how SUMOylation influences the activity of endogenous GR target genes and the receptor chromatin binding by using isogenic HEK293 cells expressing wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR). Gene expression profiling revealed that both dexamethasone up- and down-regulated genes are affected by the GR sumoylation and that the affected genes are significantly associated with pathways of cellular proliferation and survival. The GR3KR-expressing cells proliferated more rapidly and their anti-proliferative response to dexamethasone was less pronounced than in the wtGR-expressing cells. ChIP-seq analyses indicated that the SUMOylation modulates the chromatin occupancy of GR on several loci associated with cellular growth in a fashion which parallels with their differential dexamethasone-regulated expression between the two cell lines. Moreover, genome-wide SUMO-2/3 marks, which were generally associated with active chromatin, showed markedly higher overlap with the wtGR cistrome than with the GR3KR cistrome. In sum, our results indicate that the SUMOylation does not simply repress the GR activity, but regulates the activity of the receptor in a target locus selective fashion, playing an important role in controlling the GR activity on genes influencing cell growth.
Publication Title
SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
Description
Androgen receptor (AR) is typically overexpressed in castration-resistant prostate cancer (CRPC). CRPC-derived VCaP cells display an excessive number of chromatin AR-binding sites (ARBs). This study analyzed direct transcription programs of the AR, the prevalence of AR enhancers and the transcriptional regulators involved in the regulation of at the enhancer regions. The analysis utilized global nuclear run-on sequencing (GRO-seq). The GRO-seq data were integrated with the ARB and VCaP cell-specific transcription factor-binding data. Androgen in 30 min activated and repressed transcription of a large number of genes including novel AR targets IGF-1 receptor and EGF receptor. GRO-seq analysis also revealed that only a fraction of the ARBs resides at functional enhancers. Activation of AR bound enhancers was most potent at the sites that also bound PIAS1, ERG and HDAC3. Our genome-wide data provide new insights how AR can directly control growth-signaling pathways in CPRC cells. Overall design: ChIP-seq samples were collected from cells treated with vehicle (ethanol, EtOH) or 10 nM R1881 (synthetic androgen methyltrienolone). IgG sample was collected from EtOH- and R1881-treated cells and used as background control. Biological duplicate samples of the AR (R1881-treated) and CTCF (vehicle- and R1881-treated) ChIP-seq samples were analyzed by using Illumina HiSeq 2000 platform 1.9. Single IgG and H3K9me3 (R1881-treated) samples were analyzed with the same platform. GRO-seq was used to determine androgen-induced changes in nascent transcription in VCaP and LNCaP cells.
Publication Title
Global analysis of transcription in castration-resistant prostate cancer cells uncovers active enhancers and direct androgen receptor targets.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of PIAS1 co-regulation in the androgen signaling pathways in prostate cancer cell line.
Publication Title
SUMO ligase PIAS1 functions as a target gene selective androgen receptor coregulator on prostate cancer cell chromatin.
Sample Metadata Fields
Cell line, Time
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Transgenic C. elegans strains that express human SUMO-1 under the control of pan-neuronal (aex-3) or pan muscular (myo-4) promoters were assayed for gene expression changes.
Publication Title
Overexpression of SUMO perturbs the growth and development of Caenorhabditis elegans.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and -defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2 modification at K277, resulting in activation of inflammatory genes. SUMOylation of agonist-activated FXR increased its interaction with NF-B but blocked that with RXR, so that SUMO2-modified FXR was selectively recruited to and trans-repressed inflammatory genes without affecting FXR/RXR target genes. A dysregulated Acetyl/SUMO switch of FXR in obesity may serve as a general mechanism for diminished anti-inflammatory response of other transcriptional regulators and provide potential therapeutic and diagnostic targets for obesity-related metabolic disorders.
Publication Title
A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina Genome Analyzer
Description
Glucocorticoid resistance (GCR) is defined as an unresponsiveness to the anti-inflammatory properties of glucocorticoids (GCs) and their receptor, the glucocorticoid receptor (GR). It is a serious problem in the management of inflammatory diseases and occurs frequently. The strong pro-inflammatory cytokine TNF induces an acute form of GCR, not only in mice, but also in several cell lines, e.g. in the hepatoma cell line BWTG3, as evidenced by impaired Dexamethasone (Dex)-induced GR-dependent gene expression. We report that TNF has a significant and broad impact on the transcriptional performance of GR, but no impact on nuclear translocation, dimerization or DNA binding capacity of GR. Proteome-wide proximity-mapping (BioID), however, revealed that the GR interactome is strongly modulated by TNF. One GR cofactor that interacts significantly less with the receptor under GCR conditions is p300. NF?B activation and p300 knockdown both reduce transcriptional output of GR, whereas p300 overexpression and NF?B inhibition revert TNF-induced GCR, which is in support of a cofactor reshuffle model. This hypothesis is supported by FRET studies. This mechanism of GCR opens new avenues for therapeutic interventions in GCR diseases Overall design: Examination of GR induced gene expression in 4 conditions (1 control: NI and 3 treated: DEX, TNF, TNFDEX) starting from 3 biological replicates
Publication Title
TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples