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GSE22865
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Extracellular, cancer-specific methylated DNA has been shown to be a prognostic marker when detected in serum or plasma. In this study we investigated the effect of treating cancer cells with differentially methylated CpG DNA. When breast cancer cell lines were treated with methylated CpG DNA, a consistent upregulation of CHAC1 mRNA expression was observed. CHAC1 was recently described to be a novel component of the unfolded protein response pathway. To elucidate the role of CHAC1 mRNA expression in cancer in more detail, we analyzed expression of this gene in breast (n=107) and ovarian cancer (n=107) and found a strong correlation with tumor differentiation. Poorly differentiated tumors exhibited higher CHAC1 expression levels (p=0.004 for breast and p=0.031 for ovarian cancer). Additionally, hormone receptor (HR)-negative breast cancers (p<0.001) and advanced stage disease ovarian cancers (p=0.026) also demonstrated high CHAC1 mRNA levels. mRNA expression analysis of the two known CHAC1 isoforms showed a strong association of expression above the median with poor outcome in breast cancer patients in a multivariate analysis (isoform a: relative risk (RR) of death 3.2 (95% CI 1.6-6.5; p<0.01); RR of relapse 3.9 (95% CI 1.6-9.8; p<0.01); isoform b: relative risk (RR) of death 3.5 (95% CI 1.6-7.3; p<0.01); RR of relapse 6.6 (95% CI 2.4-18.5; p<0.01)). Univariate analysis in ovarian cancer showed that CHAC1 mRNA expression above the median was associated with a poor relapse free survival (p=0.03). In younger ovarian cancer patients (age < median age), a high CHAC1 mRNA expression was associated with overall survival (p=0.007) and relapse free survival (p=0.015). Finally, we show that downregulation of CHAC1 by small interfering RNA suppressed breast cancer cell migration and proliferation, whereas overexpression resulted in an observed increase in these cellular behaviours. This is the first report demonstrating that a gene (CHAC1) whose expression is triggered by methylated, but not unmethylated DNA, is involved in tumour biology.
Publication Title
Elevated mRNA expression of CHAC1 splicing variants is associated with poor outcome for breast and ovarian cancer patients.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plants regulate their time to flowering by gathering information from the environment. Photoperiod and temperature are among the most important environmental variables. Suboptimal, but not near-freezing, temperatures regulate flowering through the thermosensory pathway, which overlaps with the autonomous pathway. Here we show that ambient temperature regulates flowering by two genetically distinguishable pathways, one that requires TFL1 and another that requires ELF3. The delay in flowering time observed at lower temperatures was partially suppressed in single elf3 and tfl1 mutants, whereas double elf3 tfl1 mutants were insensitive to temperature. tfl1 mutations abolished the temperature response in cryptochrome mutants that are deficient in photoperiod perception, but not in phyB mutants that have a constitutive photoperiodic response. Contrary to tfl1, elf3 mutations were able to suppress the temperature response in phyB mutants, but not in cryptochrome mutants. The gene expression profile revealed that the tfl1 and elf3 effects are due to the activation of different sets of genes and identified CCA1 and SOC1/AGL20 as being important cross talk points. Finally, genome-wide gene expression analysis strongly suggests a general and complementary role for ELF3 and TFL1 in temperature signalling.
Publication Title
A complementary role for ELF3 and TFL1 in the regulation of flowering time by ambient temperature.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Two aspects of light are very important for plant development: the length of the light phase or photoperiod and the quality of incoming light. Photoperiod detection allows plants to anticipate the arrival of the next season, whereas light quality, mainly the red to far-red ratio (R:FR), is an early signal of competition by neighbouring plants. phyB represses flowering by antagonising CO at the transcriptional and post-translational levels. A low R:FR decreases active phyB and consequently increases active CO, which in turn activates the expression of FT, the plant florigen. Other phytochromes like phyD and phyE seem to have redundant roles with phyB. PFT1, the MED25 subunit of the plant Mediator complex, has been proposed to act in the light-quality pathway that regulates flowering time downstream of phyB. However, whether PFT1 signals through CO and its specific mechanism are unclear. Here we show that CO-dependent and -independent mechanisms operate downstream of phyB, phyD and phyE to promote flowering, and that PFT1 is equally able to promote flowering by modulating both CO-dependent and -independent pathways. Our data are consistent with the role of PFT1 as an activator of CO transcription, and also of FT transcription, in a CO-independent manner. Our transcriptome analysis is also consistent with CO and FT genes being the most important flowering targets of PFT1. Furthermore, comparison of the pft1 transcriptome with transcriptomes after fungal and herbivore attack strongly suggests that PFT1 acts as a hub, integrating a variety of interdependent environmental stimuli, including light quality and jasmonic acid-dependent defences.
Publication Title
PFT1, the MED25 subunit of the plant Mediator complex, promotes flowering through CONSTANS dependent and independent mechanisms in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Schizosaccharomyces pombe
- 5 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Positioned nucleosomes limit the access of proteins to DNA and implement regulatory features encoded in eukaryotic genomes. Here we generated the first genome-wide nucleosome positioning map for Schizosaccharomyces pombe and annotated transcription start and termination sites genome-wide. Using this resource we found surprising differences compared to the nucleosome organization in the distantly related yeast Saccharomyces cerevisiae [the cerevisiae data has been published by others (PMID: 17873876) and the raw data is deposited at ArrayExpress(E-MEXP-1172)]. DNA sequence guides nucleosome positioning differently, e.g., poly(dA:dT) elements are not enriched in S. pombe nucleosome-depleted regions (NDRs). Regular nucleosomal arrays emanate more asymmetrically, i.e., mainly co-directionally with transcription, from promoter NDRs, but promoters harbouring the histone variant H2A.Z show regular arrays also upstream. Regular nucleosome phasing in S. pombe has a very short repeat length of 154 base pairs, and requires a remodeler, Mit1, conserved in humans but not found in S. cerevisiae. Nucleosome positioning mechanisms are evidently not universal but evolutionarily plastic.
Publication Title
Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: The aim of this study is to determine the relative expresson levels of mRNA transcripts in wild type platelets Methods: Total RNA was extracted and purified from purified platelets from BALB/c male mice (3 independent samples). Platelet purification was performed as described in Josefsson EC et al, Journal of Experimental Medicine (2011) 208:2017-31. Total RNA (100 ng) was used to generate sequencing libraries for whole transcriptome analysis following Illumina’s TruSeq RNA v2 sample preparation protocol. Completed libraries were sequenced on HiSeq 2000 with TruSeq SBS Kit v3- HS reagents (Illumina) as 100 bp paired-end reads at the Australian Genome Research Facility (AGRF), Melbourne. Reads were aligned to the mouse reference genome mm10 and counts for known genes were obtained using the Rsubread package (version 1.18.0) (Liao et al. 2013; Liao et al. 2014). Overall design: Total RNA was extracted and purified from purified platelets from BALB/c male mice (3 independent samples per population).
Publication Title
Loss of PUMA (BBC3) does not prevent thrombocytopenia caused by the loss of BCL-XL (BCL2L1).
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
The goal of this study was to identify genes which are differentiatlly expresesd upon induced inactivation of Rfx6 in beta cell in adult mice Overall design: Rfx6fl/fl; Ins1-CreERT2 (mut) and Rfx6fl/fl (ctrl) 8 weeks old mice were injected subcutaneously with tamoxifen daily during 3 days. Pancreatic islets were isolated 5 days after the first injection and RNA purified.
Publication Title
Rfx6 maintains the functional identity of adult pancreatic β cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
mRNA expression profiling of pancreatic cancer, comparing adjacent normal tissue, patient tumour and first generation patient derived xenograft tumours
Publication Title
Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Here, we report on experiments in double-transgenic mice, in which RFP is expressed in all Foxp3+ Treg cells, whereas Foxp3-dependent GFP expression is exclusively confined to intrathymically induced Foxp3+ Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP+GFP+) and extrathymic (RFP+GFP) origin in otherwise unmanipulated mice.
Publication Title
Fluorochrome-based definition of naturally occurring Foxp3(+) regulatory T cells of intra- and extrathymic origin.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Analysis of Lin-c-Kit+Sca-1- haematopoietic stem cells (HSCs) expressing the Nup98-HoxD13 (NHD13) fusion gene. NHD13 induces myelodysplastic syndrome (MDS) in mice. Results provide insight into the molecular basis of the myelodysplastic phenotype Overall design: WT mouse HSCs were compared to an NHD13 mutant sequenced in triplicate on a HiSeq 2000
Publication Title
PUMA promotes apoptosis of hematopoietic progenitors driving leukemic progression in a mouse model of myelodysplasia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Whilst the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognized, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. We have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. Whilst loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. We investigated whether there were common gene expression changes between EBV-positive and loss clones derived for four endemic Burkitt lyphoma cell lines that could explain the apoptosis sensitivity of clones that had lost EBV.
Publication Title
Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells.
Sample Metadata Fields
Cell line
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