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GSE26801
Saccharomyces cerevisiae
2 Downloadable Samples
Affymetrix Yeast Genome S98 Array (ygs98)
Description
The ARV1-encoded protein mediates sterol transport from the endoplasmic reticulum (ER) to the plasma membrane. Yeast ARV1 mutants accumulate multiple lipids in the ER and are sensitive to pharmacological modulators of both sterol and sphingolipid metabolism. Using fluorescent and electron microscopy, we demonstrate sterol accumulation, subcellular membrane expansion, elevated lipid droplet formation and vacuolar fragmentation in ARV1 mutants. Motif-based regression analysis of ARV1 deletion transcription profiles indicates activation of Hac1p, an integral component of the UPR. Accordingly, we show constitutive splicing of HAC1 transcripts, induction of a UPR reporter and elevated expression of UPR targets in ARV1 mutants. IRE1, encoding the unfolded protein sensor in the ER lumen, exhibits a lethal genetic interaction with ARV1, indicating a viability requirement for the UPR in cells lacking ARV1. Surprisingly, ARV1 mutants expressing a variant of Ire1p defective in sensing unfolded proteins are viable. Moreover these strains also exhibit constitutive HAC1 splicing that interacts with DTT-mediated perturbation of protein folding. These data suggest a component of UPR induction in arv1? strains is distinct from protein misfolding. Decreased ARV1 expression in murine macrophages also results in UPR induction, particularly up-regulation of activating transcription factor-4, C/EBP homologous protein (CHOP) and apoptosis. Cholesterol loading or inhibition of cholesterol esterification further elevated CHOP expression in ARV1 knockdown cells. Thus, loss or down-regulation of ARV1 disturbs membrane and lipid homeostasis resulting in a disruption of ER integrity, one consequence of which is induction of the UPR.
Publication Title
Loss of subcellular lipid transport due to ARV1 deficiency disrupts organelle homeostasis and activates the unfolded protein response.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Decidualization is a critical process for embryo implatation during which uterine stromal fibroblasts are transformed into large, epithelioid-like decidual cell. NOTCH1 is recepotor of Notch signaling that plays important roles for cell-cell communication, which involves gene regulatory mechanisms that control multiple cellular differentiation processes during embryonic and adult life.
Publication Title
Decreased Notch pathway signaling in the endometrium of women with endometriosis impairs decidualization.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Uterine receptivity implies a dialogue between the hormonally primed maternal endometrium and the free-floating blastocyst. Endometrial stromal cells proliferate, avert apoptosis, and undergo decidualization in preparation for implantation; however, the molecular mechanisms that underlie differentiation into the decidual phenotype remain largely undefined. The Notch family of transmembrane receptors transduce extracellular signals responsible for cell survival, cell-to-cell communication, and trans-differentiation, all fundamental processes for decidualization and pregnancy. Using a murine artificial decidualization model, pharmacological inhibition of Notch signaling by gamma-secretase inhibition resulted in significantly decreased deciduoma. Furthermore, a progesterone receptor (PR)-Cre Notch1 bigenic (Notch1d/d) confirmed a Notch1-dependant hypomorphic decidual phenotype.
Publication Title
Notch1 mediates uterine stromal differentiation and is critical for complete decidualization in the mouse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Arid1a has a critical role for modulating epithelial proliferation which is a critical requisite for fertility
Publication Title
ARID1A Is Essential for Endometrial Function during Early Pregnancy.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
During the invasive phase of implantation, trophoblasts and maternal decidual stromal cells secrete products that regulate trophoblast differentiation and migration into the maternal endometrium. Paracrine interactions between the extravillous trophoblast and the maternal decidua are important for successful embryonic implantation, including establishing the placental vasculature, anchoring the placenta to the uterine wall, and promoting immuno-acceptance of the fetal allograph. Global cross-talk between the trophoblast and the decidua has not been elucidated to date, and the current study used a functional genomics approach to investigate these paracrine interactions.
Publication Title
Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of gene expresssion altered upon knockdown of histone demethylase JMJD1A in human prostate cancer cells. The objective is to elucidate the transcriptional programs that are controlled by JMJD1A in human prostate cancer.
Publication Title
Regulation of c-Myc expression by the histone demethylase JMJD1A is essential for prostate cancer cell growth and survival.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in Prostate Cancer Affecting Key Gene Networks.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Prostate cancer is the most common non-cutaneous cancer in men. The androgen receptor (AR) a ligand-activated transcription factor, constitutes the main drug target for advanced cases of the disease. However, a variety of other transcription factors and signalling networks have been shown to be altered in patients and to influence AR activity. The oncogenic transcription factor c-Myc has been studied extensively in multiple malignancies, but its impact on AR activity in prostate cancer remains elusive. In this study we assessed the impact of clinically relevant levels of c-Myc overexpression on AR activity and transcriptional output. We found that c-Myc and the AR share a substantial amount of binding sites, which exhibit enhancer-like characteristics. Interestingly, c-Myc overexpression altered global AR chromatin occupancy and antagonised a subset of androgen-induced genes. Furthermore, c-Myc overexpression modified histone marks, most notably H3K4me1 and H3K27me3. Lastly, we validated the antagonistic relationship between c-Myc and two AR target genes, KLK3 and GNMT, in patient samples.
Publication Title
c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in Prostate Cancer Affecting Key Gene Networks.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2500
Description
To determine the global effects of ASCT2 inhibition, we used next generation sequencing to determine mRNA expression changes in PC-3 cells treated with BenSer or GPNA for 48 h. Overall design: Examination of two different ASCT2 inhibitors BenSer and GPNA in prostate cancer cell line PC-3.
Publication Title
Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- IlluminaHiSeq2000
Description
Numerous chromatin-remodelling factors are regulated by interactions with RNA. However, the contexts in which chromatin-remodelling factors encounter various RNA species, as well as the molecular functions of RNA binding, are poorly understood. Here we show that R-loops, RNA:DNA hybrids consisting of nascent transcripts hybridized to template DNA strands, facilitate embryonic stem cell (ESC) differentiation by modulating the binding of two key chromatin-remodelling enzymes near gene promoters. As previously shown for polycomb repressive complex 2 (PRC2)1-5, we find that the Tip60-p400 histone acetyltransferase and nucleosome-remodelling complex binds in cis to nascent transcripts. However, whereas chromatin binding by PRC2 is broadly inhibited by transcription6, transcription is necessary for maximal Tip60-p400 binding at most target loci. Given that nascent transcripts expressed from GC-rich promoters frequently form R-loops7, we mapped the genomic locations of R-loops in mouse ESCs, observing higher average Tip60-p400 levels and lower average PRC2 levels at genes with R-loops near their transcription start sites (TSSs). Disruption of R-loops by overexpression of RNaseH1 broadly reduced Tip60-p400 and increased PRC2 enrichment, demonstrating R-loops exert both positive and negative effects on chromatin association by regulatory factors. Consistent with these findings, RNaseH1 overexpression results in widespread changes in gene expression and inhibits ESC differentiation, allowing undifferentiated cells to persist for at least two weeks after differentiation is induced. These results define a novel mechanism by which promoter-proximal R-loops modulate chromatin structure to facilitate changes in cellular identity. Overall design: We examined the transcriptional profile in control and RNaseH1 overexpression mouse ES cells during differentiation.
Publication Title
R loops regulate promoter-proximal chromatin architecture and cellular differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples