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SRP131796
Homo sapiens
8 Downloadable Samples
Illumina HiSeq 2500
Description
Steroid hormone receptors are simultaneously active in many tissues and capable of altering each other's function. Estrogen receptor ? (ER) and glucocorticoid receptor (GR) are expressed in the uterus and their ligands have opposing effects on uterine growth. In endometrial tumors expressing high levels of ER, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia. We observed low genomic binding site overlap when ER and GR are induced with their respective ligands; however, upon simultaneous induction they co-occupy more sites. GR binding is significantly altered by estradiol with GR recruited to ER bound loci that become more accessible upon estradiol induction. Gene expression responses to co-treatment were more similar to estradiol, but with novel regulated genes. Our results suggest phenotypic and molecular interplay between ER and GR in endometrial cancer. Overall design: ChIP-seq, ATAC-seq, and RNA-seq data collected from endometrial cancer cell lines induced with dexamethasone, estradiol, or the combination
Publication Title
FFPEcap-seq: a method for sequencing capped RNAs in formalin-fixed paraffin-embedded samples.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 72 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The therapy-induced PML/RARA catabolism elicits the loss of APL-initiating cell self-renewal through PML NB reformation and P53 activation. These results explain the curative activity of the RA/arsenic combination, the resistance to RA of PLZF/RARA-driven APLs and they raise the prospect that activation of this PML/P53 checkpoint might have therapeutic values in other malignancies.
Publication Title
Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus, Homo sapiens
- 30 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st), Affymetrix Mouse Gene 1.1 ST Array (mogene11st), Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PML is a ROS sensor activating p53 upon oxidative stress.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Race, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The Pml gene is essential to the formation of PML nuclear bodies, domains which have been associated with various functions such as apoptosis/senescence, DNA repair and cell proliferation( Lallemand-Breitenbach 2010). PML-NBs formation is regulated by cellular stress including oxidative stress(Jeanne 2010, de The 2012). To investigate the role of PML in ROS response in vivo, we analyse the expression difference to the acetaminophen toxicity, which is initiated by ROS, in Pml wt and Pml KO mice.
Publication Title
PML is a ROS sensor activating p53 upon oxidative stress.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Mitogen-activated protein kinases (MAPKs) regulate cardiomyocyte growth and apoptosis in response to extracellular stimulation, but the downstream effectors that mediate their pathophysiological effects remain poorly understood. We determined the targets and role of p38 MAPK in the heart in vivo by using local adenovirus-mediated gene transfer of constitutively active upstream kinase mitogen-activated protein kinase kinase 3b (MKK3bE) and wild-type p38 in rats. DNA microarray analysis of animals with cardiac-specific overexpression of p38 MAPK revealed that 264 genes were upregulated more than 2-fold including multiple genes controlling cell division, cell signaling, inflammation, adhesion and transcription. Several previously unknown p38 target genes were found. Using gel mobility shift assays we identified several cardiac transcription factors that were directly activated by p38 MAPK. Finally, we determined the functional significance of the altered cardiac gene expression profile by histological analysis and echocardiographic measurements, which indicated that p38 MAPK overexpression induced gene expression results in cell proliferation, myocardial inflammation and fibrosis. In conclusion, we defined the novel target genes and transcription factors as well as the functional effects of p38 MAPK in the heart. Expression profiling of p38 MAPK overexpression identified cell cycle regulatory and inflammatory genes critical for pathological processes in the adult heart.
Publication Title
Identification of cell cycle regulatory and inflammatory genes as predominant targets of p38 mitogen-activated protein kinase in the heart.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st), Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
The Pml gene is essential to the formation of PML nuclear bodies, domains which have been associated with various functions such as apoptosis/senescence, DNA repair and cell proliferation( Lallemand-Breitenbach 2010). PML-NBs formation is regulated by cellular stress including oxidative stress(Jeanne 2010, de The 2012). To investigate the role of PML in ROS response in vivo, we analyse the expression difference betweem Pml wt and Pml KO under fasted condition, which easily up-regulate ROS in BALB/cByJ background
Publication Title
PML is a ROS sensor activating p53 upon oxidative stress.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st), Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
PML nuclear bodies (NBs) recruit partner proteins -including p53 and its regulators- controlling their abundance or function. Investigating arsenic sensitivity of acute promyelocytic leukemia, we proposed that PML oxidation promotes NB-biogenesis. Yet, physiological links between PML and oxidative stress response in vivo remain unexplored. Here we identify PML as a reactive oxygen species (ROS) sensor. Pml-/- cells accumulate ROS, while PML expression decreases ROS levels. Unexpectedly, Pml-/- embryos survive acute glutathione depletion. Moreover, Pml-/- animals are resistant to acetaminophen hepatotoxicity or fasting-induced steatosis. Molecularly, Pml-/- animals fail to properly activate oxidative stress-responsive p53 targets, while NRF2 response is accelerated. Finally, in an oxidative stress-prone background, Pml-/- animals display a longevity phenotype, likely reflecting decreased basal p53 activation. Thus, similar to p53, PML exerts basal anti-oxidant properties, but also drives oxidative stress-induced changes in cell survival/proliferation or metabolism in vivo. Through NB-biogenesis, PML therefore couples ROS-sensing to p53 responses, shedding a new light on PML role in senescence or stem cell biology.
Publication Title
PML is a ROS sensor activating p53 upon oxidative stress.
Sample Metadata Fields
Sex, Cell line, Race, Time
View Samples- Escherichia coli
- 4 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Dynamical response to oxygen downshift under fermentation conditions was tested by taking sample before (S1) and after (S2, S3 and S4) the oxygen downshift. The dynamical changes relevant for ongoing research on physiology were applied.
Publication Title
Norvaline is accumulated after a down-shift of oxygen in Escherichia coli W3110.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Lipid-induced epigenomic changes in human macrophages identify a coronary artery disease-associated variant that regulates PPAP2B Expression through Altered C/EBP-beta binding.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The aim of the experiment was to determine the effects of 48 hours of treatment with oxidized low density lipoprotein (oxLDL) on gene expression in primary human monocyte-derived macrophages.
Publication Title
Lipid-induced epigenomic changes in human macrophages identify a coronary artery disease-associated variant that regulates PPAP2B Expression through Altered C/EBP-beta binding.
Sample Metadata Fields
Specimen part
View Samples