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GSE32892
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The androgen receptor plays a critical role throughout the progression of prostate cancer and is an important drug target for this disease. While chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-Seq) is becoming an essential tool in studying transcription and chromatin modification factors, it has rarely been employed in the context of drug discovery. Here we report the first publicly available genome-wide and dose-dependent inhibition landscape of AR binding by drug-like small molecules including correlation with binding strength using ChIP-Seq. Integration of sequence analysis, transcriptome profiling, cell viability assays and in vivo tumor inhibition studies enabled us to establish a direct cistrome-activity relationship for two novel potent AR antagonists. By selectively occupying the strongest binding sites, AR signaling remains active even when low androgen levels are low, a scenario characteristic of first-line androgen ablation therapy. Coupled cistrome and transcriptome profiling upon small molecule antagonism led to the identification of not only key direct downstream effectors of AR but also their mode of regulation: unbiased pathway mapping revealed that AR is a key modulator of steroid metabolism by forming a tightly controlled feedback loop with other nuclear receptor family members. Furthermore, we found AR has an extensive role in negative gene regulation and estrogen (related) receptor likely mediates its function as a transcriptional repressor. In conclusion, our study provides a global and dynamic view of ARs regulatory program upon antagonism, which may serve as a molecular basis for deciphering and developing AR therapeutics.
Publication Title
Dose-dependent effects of small-molecule antagonists on the genomic landscape of androgen receptor binding.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Neuronal function critically depends on coordinated subcellular distribution of mRNAs. Disturbed mRNA processing and axonal transport has been found in spinal muscular atrophy and could be causative for dysfunction and degeneration of motoneurons. Despite the advances made in characterizing the transport mechanisms of several axonal mRNAs, an unbiased approach to identify the axonal repertoire of mRNAs in healthy and degenerating motoneurons has been lacking. Here we used compartmentalized microfluidic chambers to investigate the somatodendritic and axonal mRNA content of cultured motoneurons by microarray analysis. In axons, transcripts related to protein synthesis and energy production were enriched relative to the somatodendritic compartment. Knockdown of Smn, the protein deficient in spinal muscular atrophy, produced a large number of transcript alterations in both compartments. Transcripts related to immune functions, including MHC class I genes, and with roles in RNA splicing were upregulated in the somatodendritic compartment. On the axonal side, transcripts associated with axon growth and synaptic activity were downregulated. These alterations provide evidence that subcellular localization of transcripts with axonal functions as well as regulation of specific transcripts with nonautonomous functions is disturbed in Smn-deficient motoneurons, most likely contributing to the pathophysiology of spinal muscular atrophy.
Publication Title
Subcellular transcriptome alterations in a cell culture model of spinal muscular atrophy point to widespread defects in axonal growth and presynaptic differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 124 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
The transcriptomic changes induced in the human liver cell line HepG2 by 100M menadione, 200M TBH or 50M H2O2 after treatment for 0.5, 1, 2, 4, 6, 8 and 24h.
Publication Title
Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The transcriptomics changes induced in the human liver cell line HepG2 by low and high doses of acetaminophen and solvent controls after treatment for 4 time points (12h, 24h, 48h and 72h)
Publication Title
Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 77 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 77 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Understanding toxicity pathways of engineered nanomaterials (ENM) has recently been brought forward as a key step in 21st century ENM risk assessment. Molecular mechanisms linked to phenotypic end points is a step towards the development of toxicity tests based on key events, which may allow for grouping of ENM according to their mechanisms of action. This study identified molecular mechanisms underlying mitochondrial dysfunction in human bronchial epithelial BEAS 2B cells following exposure to one of the most studied multi-walled carbon nanotubes (MWCNTs; Mitsui-7). Asbestos was used as a positive control and a non-carcinogenic glass wool material was included as a negative fibre control. Decreased mitochondrial membrane potential (MMP) was observed for MWCNTs at a biologically relevant dose (0.25 g/cm2) and for asbestos at 2 g/cm2, but not for glass wool. Extensive temporal transcriptomic and microRNA expression analyses identified a 330-gene signature related to MWCNT- and asbestos-induced MMP. Fourty-nine of the MMP-associated genes showed highly similar expression patterns over time (six time points) and the majority was found to be regulated by two transcription factors strongly involved in mitochondrial homeostasis, APP and NRF1. In addition, four miRNAs were associated with MMP and one of them, miR-1275, was found to negatively correlate with a large part of the MMP-associated genes. Cellular processes such as gluconeogenesis, glucose metabolism, mitochondrial LC-fatty acid -oxidation and spindle microtubule function were enriched among the MMP-associated genes and miRNAs. These results are expected to be useful in the identification of key events in ENM-related toxicity pathways for the development of molecular screening techniques.
Publication Title
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression profiles of Immortalized KDM5A-/- MEFs with re-introduction of wild-type KDM5A or KDM5A-H483A mutant.
Publication Title
The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 14 Downloadable Samples
Illumina HiSeq 2000
Description
To understand the function and regulation of the C. elegans heat shock factor (HSF-1) in larval development, we have used ChIP-seq to analyze the occupancy of HSF1 and RNA Pol II in L2 larvae and young adult (YA) animals grown at 20°C or upon heat shock at 34°C for 30 min. In addition, we have used RNA-seq to analyze the transcriptomes of wild type (N2), hsf-1(ok600) mutants and hsf-1(ok600); rmSi1[hsf-1::gfp] L2 larvae grown at 20°C and characterized the gene expression change by heat shock in wild type (N2) animals at L2 stage. Overall design: Experiment type: RNA-seq. Biological Source: strain: N2, OG576, AM1061; developmental dtage: L2 Larva. Experimental Factors: temperature: 20 degree celsius.
Publication Title
E2F coregulates an essential HSF developmental program that is distinct from the heat-shock response.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We used microarrays to identify genes differentially expressed between mouse RUNX2 -/- and wt embryonic humeri at stage E14.5
Publication Title
Detection of novel skeletogenesis target genes by comprehensive analysis of a Runx2(-/-) mouse model.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Goal was to detect differences in response to TLR7 versus TLR8 agonists in human monocytes from healthy donors
Publication Title
Granzyme B expression is enhanced in human monocytes by TLR8 agonists and contributes to antibody-dependent cellular cytotoxicity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples