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Saccharomyces cerevisiae
7 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Hmt1p is the predominant arginine methyltransferase in Saccharomyces cerevisiae. Its substrate proteins are involved in transcription, transcriptional regulation, nucleocytoplasmic transport and RNA splicing. Functionally, Hmt1p-catalysed methylation can also modulate protein-protein interactions. Despite Hmt1p being well-characterised, the effects of its knockout on the proteome and transcriptome have not been reported. SILAC-based analyses of the hmt1 proteome, in mid-log exponential growth, revealed a decreased abundance of phosphate-associated proteins including Pho84p (phosphate transporter), Pho8p (vacuolar alkaline phosphatase), Pho3p (acid phosphatase) along with Vtc1p, Vtc3p and Vtc4p (subunits of the vacuolar transporter chaperone complex). RNA-Seq and microarray analysis revealed a downregulation of phosphate-responsive genes in hmt1, including PHO5, PHO11 and PHO12 (acid phosphatases), PHO84 and PHO89 (phosphate transporters) and VTC3 (vacuolar transporter chaperone). Consistent with these observations, we observed a dysregulation of phosphate homeostasis in hmt1, with a general decrease in extracellular phosphatase production and a decrease in total Pi in phosphate replete medium. We show that the transcription factor Pho4p, responsible for activation of the PHO pathway, can be methylated by Hmt1p at Arg-241 and is the likely cause of phosphate dysregulation in hmt1. However, the methylation of Pho4p does not affect its nucleocytoplasmic localisation. We propose that the methylation of Pho4p may affect either its capacity to multimerise, its capacity to interact with Pho2p or target DNA, or may affect Pho4p phosphorylation at Ser-242 and/or Ser 243. Our study highlights a previously unknown function of Hmt1p in the regulation of phosphate homeostasis and suggests a means by which sensing of AdoMet may affect intracellular phosphate concentration.
Publication Title
Knockout of the Hmt1p Arginine Methyltransferase in <i>Saccharomyces cerevisiae</i> Leads to the Dysregulation of Phosphate-associated Genes and Processes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Goals and objectives of this study: to identify genes preferentially induced in human CD4+CD25hi Treg cells following T-cell activation with potential role for stabililization & maintenance of the regulatory program.
Publication Title
GARP: a key receptor controlling FOXP3 in human regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Goals and objectives of this study: to identify genes of the Treg signature induced by consitutive expression of GARP or FOXP3 in antigen-specific Th cells with potential role for stabililization & maintenance of the regulatory program.
Publication Title
GARP: a key receptor controlling FOXP3 in human regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 15 Downloadable Samples
Illumina HiSeq 2000
Description
The difference in X chromosome copy number creates a potential difference in X chromosomal gene expression between males and females. In many animals, dosage compensation mechanisms equalize X chromosome expression between sexes. Yet, X chromosome is also enriched for sex-biased genes due to differences in the evolutionary history of the X and autosomes. The manner in which dosage compensation and sex-biased gene expression exist on the X chromosome remains an open question. Most studies compare gene expression between two sexes, which combines expression differences due to X chromosome number (dose) and sex. Here, we uncoupled the effects of sex and X dose in C. elegans and determined how each process affects expression of the X chromosome compared to autosomes. We found that in the soma, sex-biased expression on the X chromosome is almost entirely due to sex because the dosage compensation complex (DCC) effectively compensates for the X dose difference between sexes. In the germline where the DCC is not present, X chromosome copy number contributes to hermaphrodite-biased gene expression. These results suggest that X dose contributes to sex-biased gene expression based on the level of dosage compensation in different tissues and developmental stages. Overall design: RNA-Seq profiles of C. elegans XO hermaphrodite and XX male L3 larvae and adults
Publication Title
Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The clinical efficacy of EGFR kinase inhibitors gefitinib and erlotinib is limited by the development of drug resistance. The most common mechanism of drug resistance is the secondary EGFR T790M mutation. Strategies to overcome EGFR T790M mediated drug resistance include the use of mutant selective EGFR inhibitors, including WZ4002, or by the use of high concentrations of irreversible quinazoline EGFR inhibitors such as PF299804. In the current study we develop drug resistant versions of the EGFR mutant PC9 cell line which reproducibly develops EGFR T790M as a mechanism of drug resistance to gefitinib. Neither PF299804 resistant (PFR) or WZ4002 resistant (WZR) clones of PC9 harbor EGFR T790M. Instead, they demonstrate activated IGF1R signaling as a result of loss of expression of IGFBP3 and the IGF1R inhibitor, BMS 536924, restores EGFR inhibitor sensitivity. Intriguingly, prolonged exposure to either PF299804 or WZ4002 results in the emergence of a more drug resistant subclone which contains ERK activation. A MEK inhibitor, CI-1040, partially restores sensitivity to EGFR/IGF1R inhibitor combination. Moreover, an IGF1R or MEK inhibitor used in combination with either PF299804 or WZ4002 completely prevents the emergence of drug resistant clones in this model system. Our studies suggest that more effective means of inhibiting EGFR T790M will prevent the emergence of this common drug resistance mechanism in EGFR mutant NSCLC. However, multiple drug resistance mechanisms can still emerge. Preventing the emergence of drug resistance, by targeting pathways activated in resistant cancers before they emerge, may be a more effective clinical strategy.
Publication Title
Resistance to irreversible EGF receptor tyrosine kinase inhibitors through a multistep mechanism involving the IGF1R pathway.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Analysis of gene expression in the meristematic zone of Arabidopsis roots overexpressing miR396
Publication Title
MicroRNA miR396 Regulates the Switch between Stem Cells and Transit-Amplifying Cells in Arabidopsis Roots.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
At present, medical treatments of synchronous and metachronous liver metastases from colorectal cancer are not differentiated. The aim of the study was to analyze the gene expression profiling of synchronous and metachronous lesions in order to identify molecular signatures as possible basis for choice of systemic therapies. Fresh tissues specimens from metastases of 18 patients undergone liver surgery were collected (10 synchronous and 8 metachronous lesions). Gene expression profiling was studied using Affymetrix platform. Two different profiles were identified. Pathway related to the Epidermal Growth Factor receptor (EGFr) was upregulated in metachronous lesions whereas pathways mainly related to inflammation in synchronous lesions. Real Time-PCR, Western Blotting and ELISA confirmed that the metachronous lesions had the overexpression of EGFr, but the synchronous ones had the overexpression of Cyclo-oxygenase 2 (COX-2). These results suggest that synchronous or metachronous liver metastases from colorectal cancer could be differently treated on the basis of different molecular pathways.
Publication Title
Gene expression profiling of liver metastases from colorectal cancer as potential basis for treatment choice.
Sample Metadata Fields
Specimen part
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GSE30761- Mus musculus, Mus musculus x mus spretus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 45 Downloadable Samples
- IlluminaGenomeAnalyzer
Description
Expression levels of human genes vary extensive among individuals. Gene expression determines cell function and characteristics thus this variation likely contributes to phenotypic variation. Genetic studies have shown that there is a heritable component to gene expression variation, and have identified genomic regions that contain polymorphic regulators. However, most of these regions are quite large, and few regulators have been identified. In this genetic of gene expression study, we used a large sample to search the genome for polymorphic regulators that influence gene expression, and followed up the results with deep sequencing of transcriptomes and molecular analyses. Key word(s): Transcriptome Analysis Overall design: genetics of gene expression study, 41 Coriell cell line samples examined.
Publication Title
Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 14 Downloadable Samples
- Illumina Genome Analyzer II
Description
Both transcription and post-transcriptional processes, such as alternative splicing, play crucial roles in controlling developmental programs in metazoans. Recently emerged RNA-seq method has brought our understanding of eukaryotic transcriptomes to a new level, because it can resolve both gene expression level and alternative splicing events simultaneously. To gain a better understanding of cellular differentiation in gonads, we analyzed mRNA profiles from Drosophila testes and ovaries using RNA-seq. We identified a set of genes that have sex-specific isoforms in wild-type (WT) gonads, including several transcription factors. We found that differentiation of sperms from undifferentiated germ cells induced a dramatic downregulation of RNA splicing factors. Our data confirmed that RNA splicing events are significantly more frequent in the undifferentiated cell-enriched bag of marbles (bam) mutant testis, but downregulated upon differentiation in WT testis. Consistent with this, we showed that genes required for meiosis and terminal differentiation in WT testis were mainly regulated at the transcriptional level, but not by alternative splicing. Unexpectedly, we observed an increase in expression of all families of chromatin remodeling factors and histone modifying enzymes in the undifferentiated cell-enriched bam testis. More interestingly, chromatin regulators and histone modifying enzymes with opposite enzymatic activities are coenriched in undifferentiated cells in testis, suggesting that these cells may possess dynamic chromatin architecture. Finally, our data revealed many new features of the Drosophila gonadal transcriptomes, and will lead to a more comprehensive understanding of how differential gene expression and splicing regulate gametogenesis in Drosophila. Our data provided a foundation for the systematic study of gene expression and alternative splicing in many interesting areas of germ cell biology in Drosophila, such as the molecular basis for sexual dimorphism and the regulation of the proliferation vs terminal differentiation programs in germline stem cell lineages. Overall design: RNA-Seq experiments for four Drosophila melanogaster samples: (1) bam mutant testes, (2) wild-type testes, (3) bam mutant ovaries, (4) wild-type ovaries
Publication Title
Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster.
Sample Metadata Fields
Specimen part, Subject
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