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GSE59385
Homo sapiens
12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
We previously identified the ZTRE in genes involved in zinc homeostasis and showed that it mediates transcriptional repression in response to zinc. We now report that ZNF658 acts at the ZTRE. ZNF658 was identified by MALDI-TOF mass spectrometry of a band excised after EMSA using a ZTRE probe. The protein contains a KRAB domain and 21 zinc fingers. It has similarity with ZAP1 from Saccharomyces cerevisiae, which regulates the response to zinc restriction, including a conserved DNA binding region we show to be functional also in ZNF658. siRNA targeted to ZNF658 abrogated the zinc-induced, ZTRE-dependent reduction in SLC30A5 (ZnT5), SLC30A10 (ZnT10) and CBWD transcripts in human Caco-2 cells and the ability of zinc to repress reporter gene expression from corresponding promoter-reporter constructs. Microarray analysis of the effect of reducing ZNF658 expression by siRNA uncovered large changes in rRNA. We find that ZTREs are clustered within the 45S rRNA precursor. We also saw effects on expression of multiple ribosomal proteins. ZNF658 thus links zinc homeostasis with ribosome biogenesis, the most active transcriptional, and hence zinc-demanding, process in the cell. ZNF658 is thus a novel transcriptional regulator that plays a fundamental role in the orchestrated cellular response to zinc availability.
Publication Title
The zinc finger protein ZNF658 regulates the transcription of genes involved in zinc homeostasis and affects ribosome biogenesis through the zinc transcriptional regulatory element.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 336 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Enhanced stability of microRNA expression facilitates classification of FFPE tumour samples exhibiting near total mRNA degradation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Mice lacking p53 and one or two alleles of the cyclin D-dependent kinase inhibitor p18Ink4c are prone to medulloblastoma development. The tumor frequency is increased by exposing postnatal animals to ionizing radiation at a time when their cerebella are developing. In irradiated mice engineered to express a floxed p53 allele and a Nestin-Cre transgene, tumor development can be restricted to the brain. Analysis of these animals indicated that inactivation of one or both Ink4c alleles did not affect the time of medulloblastoma onset but increased tumor invasiveness. All such tumors exhibited complete loss of function of the Patched 1 (Ptc1) gene encoding the receptor for sonic hedgehog, and many exhibited other recurrent genetic alterations, including trisomy of chromosome 6, amplification of N-Myc, modest increases in copy number of the Ccnd1 gene encoding cyclin D1, and other complex chromosomal rearrangements. In contrast, medulloblastomas arising in Ptc1+/- mice lacking one or both Ink4c alleles retained p53 function and exhibited only limited genomic instability. Nonetheless, complete inactivation of the wild type Ptc1 allele was a universal event, and trisomy of chromosome 6 was again frequent. The enforced expression of N-Myc or cyclin D1 in primary cerebellar granule neuron precursors isolated from Ink4c-/-, p53-/- mice enabled the cells to initiate medulloblastomas when injected back into the brains of immunocompromised recipient animals. These engineered tumors exhibited gene expression profiles indistinguishable from those of medulloblastomas that arose spontaneously. These results underscore the functional interplay between a network of specific genes that recurrently contribute to medulloblastoma formation.
Publication Title
Genetic alterations in mouse medulloblastomas and generation of tumors de novo from primary cerebellar granule neuron precursors.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa pao1, Pseudomonas aeruginosa
- 16 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
NextSeq 550, Illumina HiSeq 2500
Description
The Drosophila wing disc has been a fundamental model system for the discovery of key signaling pathways and for our understanding of developmental processes. However, a complete map of gene expression in this tissue is lacking. To obtain a complete gene expression atlas in the wing disc, we employed single-cell sequencing (scRNA-seq) and developed a new method for analyzing scRNA-seq data based on gene expression correlations rather than cell mappings. This enables us to discover 824 genes with spatially restricted expression patterns, and to compute expression maps for all genes in the wing disc. This approach identifies both known and new clusters of genes with similar expression patterns and functional relevance. As proof of concept, we characterize the previously unstudied gene CG5151 and show it regulates Wnt signaling. This novel method will enable the leveraging of scRNA-seq data for generating expression atlases of undifferentiated tissues during development. Overall design: Single cell transcriptome experiments from female wandering 3rd instar wing discs were generated: two samples using Drop-seq and one sample using the 10x genomics platform. Bulk polyA-RNA-seq experiment from the same tissue was conducted for comparison.
Publication Title
Gene expression atlas of a developing tissue by single cell expression correlation analysis.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Pseudomonas aeruginosa pao1, Pseudomonas aeruginosa
- 8 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The opportunistic human pathogen Pseudomonas aeruginosa can utilize several carbon and nitrogen compounds as energy sources, which allows the bacterium to grow on a variety of different environments. Nevertheless, the uptake and utilization of these compounds is organized in a hierarchical manner, which is guaranteed by a mechanism named catabolite repression. In P. aeruginosa catabolite repression is a post-transcriptional process with the translational repressor protein, Crc, as the main component. Crc recognizes CA-motifs (acronym for catabolite activity) present in the vicinity of the ribosome binfing site of corresponding target mRNAs and therefore compete with ribosome binding. Certain conditions, which are mainly related to changes in the carbon to nitrogen ratio, induce the two component system CbrAB, which activates the transcription of the sRNA CrcZ. The sRNA sequesters Crc and allows the translation of the target mRNAs. The main focus of this study was to identify novel direct targets of the CbrAB/Crc system with the use of a transcriptome analysis in combination with the search for CA-motifs. We were able to identify five novel targets (estA, acsA, dctP, bkdR and aroP2), which were involved in the uptake and utilization of less preferred carbon sources and amino acids. Direct interaction of Crc with these genes and the resulting regulation by CbrB and CrcZ were verified using mutational analysis and in vitro and in vivo experiments. Moreover, these targets were discussed in the light of growth and biofilm development in synthetic CF sputum medium which emphasised the importance of the CbrAB/Crc system as a regulator of chronic infection.
Publication Title
Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa pao1, Pseudomonas aeruginosa
- 8 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The opportunistic human pathogen Pseudomonas aeruginosa can utilize several carbon and nitrogen compounds as energy sources, which allows the bacterium to grow on a variety of different environments. Nevertheless, the uptake and utilization of these compounds is organized in a hierarchical manner, which is guaranteed by a mechanism named catabolite repression. In P. aeruginosa catabolite repression is a post-transcriptional process with the translational repressor protein, Crc, as the main component. Crc recognizes CA-motifs (acronym for catabolite activity) present in the vicinity of the ribosome binfing site of corresponding target mRNAs and therefore compete with ribosome binding. Certain conditions, which are mainly related to changes in the carbon to nitrogen ratio, induce the two component system CbrAB, which activates the transcription of the sRNA CrcZ. The sRNA sequesters Crc and allows the translation of the target mRNAs. The main focus of this study was to identify novel direct targets of the CbrAB/Crc system with the use of a transcriptome analysis in combination with the search for CA-motifs. We were able to identify five novel targets (estA, acsA, dctP, bkdR and aroP2), which were involved in the uptake and utilization of less preferred carbon sources and amino acids. Direct interaction of Crc with these genes and the resulting regulation by CbrB and CrcZ were verified using mutational analysis and in vitro and in vivo experiments. Moreover, these targets were discussed in the light of growth and biofilm development in synthetic CF sputum medium which emphasised the importance of the CbrAB/Crc system as a regulator of chronic infection.
Publication Title
Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Degradation and chemical modification of RNA in formalin-fixed paraffin-embedded (FFPE) samples hamper their use in expression profiling studies. In this study, we investigated the feasibility of gene expression signature generation from archival FFPE materials. Nineteen cervical squamous cell carcinoma (SCC) and nine adenocarcinoma (AC) 10~16-year-old FFPE samples were profiled using Affymetrix Exon 1.0 ST arrays. A comparison of the global gene expression changes between SCC and AC revealed 1217 differentially expressed genes. Of these, 1062 showed significantly higher expression levels in SCC relative to AC, and 155 genes were found to be specifically upregulated in AC. When the 1217-gene signature was tested on a fresh-frozen human non-small cell lung cancer (NSCLC) series, it correctly separated the 58 NSCLC samples into SCC and AC. In conclusion, our results showed that clinically and biologically relevant gene expression profiles can be derived from FFPE samples with Exon array profiling.
Publication Title
Exon-array profiling unlocks clinically and biologically relevant gene signatures from formalin-fixed paraffin-embedded tumour samples.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Background: pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood.
Publication Title
Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples