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GSE113945
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Heterozygosity for human STAT3 dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-IgE syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341. ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including, most notably the STAT3 promoter. The patients cells have low basal levels of STAT3 mRNA and protein. The auto-induction of STAT3 production, activation, and function by STAT3-activating cytokines is particularly strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack Th17 cells, have an excess of Th2 cells, and low memory B cells, due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341-dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription-dependent auto-induction and sustained activity of STAT3.
Publication Title
A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 132 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
DNA repair is an essential cellular process required to maintain genomic stability. Every cell is subjected to thousands of DNA lesions daily under normal changes in transcription. Transcription is a primary process where protein amount and function can be regulated. One aspect of the transcriptional IR response that little is known about on a whole genome basis is alternative transcription. These investigations focus on the response to IR at the exon level in human cells but also at the whole gene level. Whole genome exon arrays were utilized to comprehensively characterize radiation-induced transcriptional expression products in two human cell types, namely EBV-transformed lymphoblast and primary fibroblast cell lines.
Publication Title
DNA repair genes: alternative transcription and gene expression at the exon level in response to the DNA damaging agent, ionizing radiation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The LEF/TCF family of transcription factors are downstream effectors of the WNT signaling pathway, which drives colon tumorigenesis. LEF/TCFs have a DNA sequence-specific HMG box that binds Wnt Response Elements (WREs). The E tail isoforms of TCFs are alternatively spliced to include a second DNA binding domain called the C-clamp. We show that induction of a dominant negative C-clamp version of TCF1 (dnTCF1E) induces a p21-dependent stall in the growth of DLD1 colon cancer cells. Induction of a C-clamp mutant did not induce p21 or stall cell growth. Microarray analysis revealed that induction of p21 by dnTCF1EWT correlated with a decrease in expression of p21 suppressors that act at multiple levels from transcription (SP5, YAP1, RUNX1), to RNA stability (MSI2), and protein stability (CUL4A). We show that the C-clamp is a sequence specific DNA binding domain that can make contacts with 5-RCCG-3 elements upstream or downstream of WREs. The C-clamp-RCCG interaction was critical for TCF1E mediated transcriptional control of p21-connected target gene promoters. Our results indicate that a WNT/p21 circuit is driven by C-clamp target gene selection.
Publication Title
A WNT/p21 circuit directed by the C-clamp, a sequence-specific DNA binding domain in TCFs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Peripheral whole blood-based gene expression profiling has become one of the most common strategies exploited in the development of clinically relevant biomarkers. However, the ability to identify biologically meaningful conclusions from gene expression patterns in whole blood is highly problematic. First, it is difficult to know whether or not expression patterns in whole blood capture those in primary tissues. Second, if explicit steps are not taken to accommodate the extremely elevated expression levels of globin in blood then large-scale multi-probe microarray-based studies can be severely compromised. Many studies consider the use of mouse blood as a model for human blood in addition to considering blood gene expression levels as a general surrogate for gene expression levels in other tissues. We explored the effects of globin reduction on peripheral mouse blood in the detection of genes known to be expressed in human tissues. Globin reduction resulted in 1.) a significant increase in the number of probes detected (5840 944 vs 12411 1904); 2.) increased expression for 4128 probe sets compared to non-globin reduced blood (p < .001, two-fold); 3.) improved detection of genes associated with many biological pathways and diseases; and 4.) an increased ability to detect genes expressed in 27 human tissues (p < 10-4). This study suggests that although microarray-based mouse blood gene expression studies that do not consider the effects of globin are severely compromised, globin-reduced mouse whole blood gene expression studies can be used to capture the expression profiles of genes known to contribute to various human diseases.
Publication Title
The effects of globin on microarray-based gene expression analysis of mouse blood.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 50 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Fetal asphyctic (FA) preconditioning is effective in attenuating brain damage incurred by a subsequent perinatal asphyctic insult. Unraveling mechanisms of this endogenous neuroprotection, activated by FA preconditioning, is an important step towards new clinical strategies for asphyctic neonates. Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of preconditioning. Therefore, we investigated whole genome differential expression in the preconditioned rat brain.
Publication Title
Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
High-throughput systems for gene expression profiling have been developed and matured rapidly through the past decade. Broadly, these can be divided into two categories: hybridization-based and sequencing-based approaches. With data from different technologies being accumulated, concerns and challenges are raised regarding data comparability and agreement across technologies. Within an ongoing large-scale cross-platform data comparison framework, we report here a comparison based on identical samples between one-dye DNA microarray platforms and MPSS (Massively Parallel Signature Sequencing). The DNA microarray platforms generally provided highly correlated data, while moderate correlations between microarrays and MPSS were obtained. Disagreements between the two types of technologies can be attributed to limitations inherent to both technologies. The variation found between pooled biological replicates underlines the importance of exercising caution in identification of differential expression, especially for the purposes of biomarker discovery. Based on different principles, hybridization-based and sequencing-based technologies should be considered complementary to each other, rather than competitive, and currently, both provide indispensable tools for transcriptome profiling.
Publication Title
Comparison of hybridization-based and sequencing-based gene expression technologies on biological replicates.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The glucocorticoid receptor overexpression in early life is sufficient to alter gene expression patterns for the rest of the animal's life.
Publication Title
Early-life forebrain glucocorticoid receptor overexpression increases anxiety behavior and cocaine sensitization.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarray analysis to profile the function of TCF7L1 in human embryonic stem cells.
Publication Title
TCF7L1 suppresses primitive streak gene expression to support human embryonic stem cell pluripotency.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarray analysis to profile the function of TCF7L1 in human embryonic stem cells.
Publication Title
TCF7L1 suppresses primitive streak gene expression to support human embryonic stem cell pluripotency.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The first week of human pre-embryo development is characterized by the induction of totipotency and then pluripotency. The understanding of this delicate process will have far reaching implication for in vitro fertilization and regenerative medicine. Human mature MII oocytes and embryonic stem (ES) cells are both able to achieve the feat of cell reprogramming towards pluripotency, either by somatic cell nuclear transfer or by cell fusion, respectively. Comparison of the transcriptome of these two cell types may highlight genes that are involved in pluripotency initiation. Therefore, based on a microarray compendium of 205 samples, produced in our laboratory or from public databases, we compared the gene expression profile of mature MII oocytes and human ES cells (hESC) to that of somatic tissues. We identified a common oocyte/hESC gene expression profile, which included a strong cell cycle signature, a large chromatin remodelling network (TOP2A, DNMT3B, JARID2, SMARCA5, CBX1, CBX5) and 18 different zinc finger transcription factors, including ZNF84. Strikingly, a large set of genes was found to code for proteins involved in the ubiquitination and proteasome pathway. Upon hESC differentiation into embryoid bodies, the transcription of this pathway declines. In vitro, we observed a selective sensitivity of hESC to the inhibition of the activity of the proteasome, resulting in loss of pluripotency and cell growth at doses without any detectable effects on differentiated cells. Taken together, these results suggest that the proteasome pathway may play a role in initiating and maintaining pluripotency during early development and in hESC.
Publication Title
A gene expression signature shared by human mature oocytes and embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples