Filters
Technology
Platform
GSE18488
Saccharomyces cerevisiae
14 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Sir2 is an NAD+-dependent histone deacetylase, and is the founding member of a large, phylogentically conserved, family of such deacetylases called the Sirtuins. The budding yeast, Saccharomyces cerevisiae, harbors 4 paralogs of Sir2, known as Hst1, Hst2, Hst3, and Hst4. Reducing the intracellular NAD+ concentration is inhibitory for the Sirtuins, and raising the intracellular nicotinamide (NAM) concentration is inhibitory. Microarray gene expression analysis was used to identify novel classes of yeast genes whose expression is altered when either NAD+ concentration is reduced or NAM is elevated. A subset of genes involved in thiamine biosynthesis was identified as being upregulated when Sir2 or Hst1 was inactivated.
Publication Title
Thiamine biosynthesis in Saccharomyces cerevisiae is regulated by the NAD+-dependent histone deacetylase Hst1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PPARG binding landscapes in macrophages suggest a genome-wide contribution of PU.1 to divergent PPARG binding in human and mouse.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Genome-wide comparisons of transcription factor binding sites in different species allow for a direct evaluation of the evolutionary constraints that shape transcription factor binding landscapes. To gain insights into the evolution of the PPARg-dependent transcriptional network we obtained binding data for PPARg, RXR and PU.1 in human macrophages and compared the profiles to matching data from mouse macrophages. We found that PPARg binding was highly divergent and only 5% of the PPARg bound regions were occupied in both species. Despite the low conservation of PPARg binding sites, conserved PPARg target genes contribute more than 30% to the functional target genes identified in human macrophages. In addition conserved target genes are strongly enriched for lipid metabolic functions. We detected the lineage-specification factor PU.1 at the majority of human PPARg binding sites. This confirmed the juxtaposed binding configuration found in mouse macrophages and demonstrated the preservation of tissue-specific adjacent PPARg-Pu.1 binding in the absence of individual binding site conservation. Finally, based on this of PPARg and PU.1 binding between human and mouse we suggest a mechanism by which PU.1 facilitates PPARg binding site turnover in macrophages.
Publication Title
PPARG binding landscapes in macrophages suggest a genome-wide contribution of PU.1 to divergent PPARG binding in human and mouse.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The effects of LXR stimulation by GW3965 treatment on global mRNA and miRNA expression in primary human in vitro differentiated adipocytes was investigated using microarray profiling.
Publication Title
LXR is a negative regulator of glucose uptake in human adipocytes.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
EphB receptors regulate the proliferation and positioning of intestinal stem and progenitor cells. In addition, they can act as tumor promoters for adenoma development, but suppress progression to invasive carcinoma. Here we used imatinib to abrogate Abl kinase activity in ApcMin/+ mice and in mice with LGR5+ stem cells genetically targeted for APC. This treatment inhibited the tumor-promoting effects of EphB signaling without attenuating EphB-mediated tumor suppression, demonstrating the role of EphB signaling in intestinal tumor initiation. The investigated treatment regimen extended the lifespan of ApcMin/+ mice, and reduced cell proliferation in cultured slices of adenomas from FAP patients. These findings connect the EphB signaling pathway to the regulation of intestinal adenoma initiation via Abl kinase. Our findings may have clinical implications for pharmacological therapy against adenoma formation and cancer progression in patients predisposed to develop colon cancer.
Publication Title
An EphB-Abl signaling pathway is associated with intestinal tumor initiation and growth.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
In order to define the targets of two miRNA overexpressed in NK cells in CFS/ME paitents, miRNA precursors for hsa-miR-99b and hsa-miR-330-3p were transfected in to buffy coat derived Natural Killer cells isolated by negative magnetic selection.
Publication Title
MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME).
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Multiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and re-populate the tumor. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and re-activation. In this study we track individual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state which is switched on by engagement with bone lining cells or osteoblasts, and switched off by osteoclasts remodeling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy targeting dividing cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.
Publication Title
Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
The peroxisome proliferator-activated receptor-coactivator-11 (PGC-11) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-11 activation has been suggested to be beneficial for systemic metabolism. Pharmacological PGC-11 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-11 is a transcriptional coactivator with no known ligand-binding activities. Importantly, PGC-11 activation is regulated by several mechanisms but protein stabilization is a limiting step as the protein has a short half-life under unstimulated conditions.
Publication Title
Small molecule PGC-1α1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
To test the effect of silencing Rae1 on expression on RNA polymerase II transcripts, host mRNAs were analysed by cDNA microarrays. We hypothesized that if silencing Rae1 expression increases cellular resistance to inhibition of transcription in VSV infected cells, mRNA characteristic of host antiviral response would be increased than compared to cells transfected with control siRNA.
Publication Title
Complexes of vesicular stomatitis virus matrix protein with host Rae1 and Nup98 involved in inhibition of host transcription.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Integration of high-risk human papillomavirus (HRHPV) into the host genome is a key event in cervical neoplastic progression. Integration is associated with deregulated expression of the viral oncogenes E6 and E7 and acquisition of a selective growth advantage for cells containing integrants. Overexpression of the viral transcriptional regulator E2 from heterologous promoters has an inhibitory effect on transcription from integrated HRHPV. We therefore hypothesised that loss of E2-expressing episomes from cells in which integration had previously occurred would be required for such cells to gain a growth advantage. Using the unique W12 model of cervical squamous carcinogenesis, we show that cells containing integrated HPV16 reproducibly emerged during long-term culture when there had been a rapid fall in episome numbers. During the period of emergence it is possible to isolate single-cell clones containing an intracellular mixture of the integrant being selected and episomes at reduced load. Microarray analysis showed that episome loss was closely associated with endogenous activation of antiviral response genes that are also inducible by the type I interferon (IFN) pathway. Taken together, our results indicate that episome loss, associated with induction of antiviral response genes, is a key event in the spontaneous selection of cervical keratinocytes containing integrated HPV16. We conclude that cervical carcinogenesis requires not only HRHPV integration, but also loss of inhibitory episomes.
Publication Title
Selection of cervical keratinocytes containing integrated HPV16 associates with episome loss and an endogenous antiviral response.
Sample Metadata Fields
No sample metadata fields
View Samples