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GSE8388
Homo sapiens
24 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
A unique feature of the tumour cells (Hodgkin/Reed-Sternberg (HRS)) of classical Hodgkin lymphoma (cHL) is the loss of their B-cell phenotype despite their B-cell origin. Several lines of evidence suggest that epigenomic events, especially promoter DNA-methylation, are involved in this silencing of many B-cell associated genes. Here we show that DNA-demethylation alone or in conjunction with histone-acetylation is not able to reconstitute the B-cell gene expression program in cultured HRS cells. Instead, combined DNA-demethylation and histone-acetylation of B cells induce a nearly complete extinction of their B-cell expression program and a tremendous up-regulation of numerous cHL characteristic genes including key players such as Id2 known to be involved in the suppression of the B-cell phenotype. Since the up-regulation of cHL characteristic genes and the extinction of the B-cell expression program occurred simultaneously, epigenetic changes may also be responsible for the malignant transformation of cHL. The epigenetic up-regulation of cHL characteristic genes thus play - in addition to promoter DNA-hypermethylation of B-cell associated genes a pivotal role for the reprogramming of HRS cells and explain why DNA-demethylation alone is unable to reconstitute the B-cell expression program in HRS cells.
Publication Title
Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In lymphomas derived from mature B cells the expression of the transcription factor PAX5 is maintained whereas classical Hodgkin lymphoma displays significantly reduced PAX5 expression despite its derivation from mature B cells. To elucidate the functional role of PAX5 in classical Hodgkin lymphoma, we re-established the PAX5 expression in the Hodgkin cell line L428 with and without epigenetic modulation. To this end, we stably transfected the Hodgkin cell line L428 with an inducible PAX5 expression construct. Although the overexpressed PAX5 was transcriptionally active as demonstrated by synthetic reporter constructs, no induction of the B-cell phenotype was achieved. PAX5 chromatin immunoprecipitation with subsequent next generation sequencing in B-cell lines and the PAX5 overexpressing L428 cell line showed different binding patterns. Since epigenetic restrictions might affect PAX5 binding, combined DNA demethylation and histone acetylation was performed. However, no re-expression of B-cell genes was observed also under these conditions. Thus, PAX5 is not sufficient for the re-activation of the B-cell program in Hodgkin cells despite epigenetic opening of the chromatin. This clearly indicates that the repression of the B-cell identity of the Hodgkin cells is caused and secured by complex molecular mechanisms.
Publication Title
PAX5 overexpression is not enough to reestablish the mature B-cell phenotype in classical Hodgkin lymphoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background
Publication Title
Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background
Publication Title
Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background
Publication Title
Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background: MYC is a transcription factor encoded by the c-MYC gene (thereafter termed MYC). MYC is key transcription factor involved in many central cellular processes including ribosomal biogenesis. MYC is overexpressed in the majority of human tumours including aggressive B-cell lymphoma especially Burkitt's lymphoma. Although Burkitt's lymphoma is a highlight example for MYC overexpression due to a chromosomal translocation, no global analysis of MYC binding sites by chromatin immunoprecipitation (ChIP) followed by global next generation sequencing (ChIP-Seq) has been conducted so far in Burkitt's lymphoma.
Publication Title
Deep sequencing of MYC DNA-binding sites in Burkitt lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Background
Publication Title
mRNA levels in control rat liver display strain-specific, hereditary, and AHR-dependent components.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 11 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Idiosyncratic drug reactions (IDRs) cause significant morbidity and mortality. In an animal model of IDRs, 50-80% of Brown Norway rats exposed to D-penicillamine develop an autoimmune syndrome after several weeks of treatment. The symptoms of the IDR are similar to that observed in humans who take D-penicillamine. The mechanism of this reaction is unknown, and no effective biomarkers have been identified to predict susceptibility. We postulate that cell stress caused by drugs is required to initiate the response. We used a highthroughput approach to identify factors that might represent danger signals by profiling hepatic gene expression 6 h after dosing with D-penicillamine (150 mg/kg). Our results show that the drug-treated animals cluster into two distinct groups. One group exhibits substantial expression changes relative to control animals. The most significantly altered transcripts have a role in stress, energy metabolism, acute phase response, and inflammation. We used quantitative reverse transcriptase polymerase chain reaction to measure transcript levels in liver biopsies of 33 rats and found that resistant animals cluster together. This 'resistant' cluster of animals contains 87.5% (7/8) resistant animals but only 48% (12/25) 'sensitive' animals. This separation is statistically significant at the p 0.01 level.
Publication Title
Gene expression profiling in a model of D-penicillamine-induced autoimmunity in the Brown Norway rat: predictive value of early signs of danger.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Rattus norvegicus
- 39 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Major toxicities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) result from dysregulation of gene expression mediated by the aryl hydrocarbon receptor (AHR). Dioxin-like chemicals alter expression of numerous genes in liver but the specific genes whose dysregulation leads to toxicities such as wasting, hepatotoxicity and lethality have not been identified. We searched for genes that are most likely to be key to dioxin toxicity by using gene expression arrays to contrast hepatic gene expression after TCDD treatment in dioxin-sensitive rats (that carry wildtype AHR) with gene expression in H/W(Kuopio) rats which are highly resistant to dioxin toxicity due to a major deletion in the AHR's transactivation domain (TAD). The total number of TCDD-responsive genes was smaller in rats with the AHRH/W genotype than in rats with wildtype AHR. However, genes in the classic AH gene battery such as CYP1A1, CYP1A2 and CYP1B1 remained fully responsive to TCDD in AHRH/W rats; thus the TAD deletion selectively interferes with expression of a subset of hepatic genes rather than abolishing global AHR-mediated responses. Genes in the following functional categories differ in response to TCDD between dioxin-sensitive rats and dioxin-resistant rats: fatty acid oxidation, metabolism (xenobiotic, alcohol, amino acid, and fatty acid), phosphate transport, regulation of steroid biosynthesis, nitrogen compound catabolism, and generation of precursor metabolites and energy. Many of these differentially-responsive genes are integral parts of pathways such as: protein degradation and synthesis, fatty acid metabolism and synthesis, cytokinesis, cell growth, and apoptosis which may be part of mechanisms which lead to TCDD-induced wasting, hepatotoxicity, tumors, and death. These differentially-responsive genes are worthy candidates for further mechanistic studies to test their role in mediating or protecting from major dioxin toxicities.
Publication Title
Aryl hydrocarbon receptor (AHR)-regulated transcriptomic changes in rats sensitive or resistant to major dioxin toxicities.
Sample Metadata Fields
No sample metadata fields
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