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GSE23711
Saccharomyces cerevisiae
6 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The basic unit of genome packaging is the nucleosome, and nucleosomes have long been proposed to restrict DNA accessibility both to damage and to transcription. However, nucleosome number in cells was considered fixed, and no condition was described where nucleosome number was reduced. We show here that mammalian cells lacking High Mobility Group Box 1 protein (HMGB1) contain a reduced amount of core, linker and variant histones, and a correspondingly reduced number of nucleosomes. Yeast nhp6 mutants lacking NHP6A and B proteins, which are related to HMGB1, also have a reduced amount of histones and fewer nucleosomes. Nucleosome limitation in both mammalian and yeast cells increases the sensitivity of DNA to damage, increases transcription globally, and the relative expression of about 10% of genes. In yeast nhp6 cells the loss of more than one nucleosome in four does not affect the location of nucleosomes and their spacing, but nucleosomal occupancy. The decrease in nucleosomal occupancy is non-uniform, and our results can be modelled assuming that different nucleosomal sites compete for the available histones: sites with high affinity are almost always packaged into nucleosomes both in wt and nucleosome-depleted cells, whereas sites with low affinity are less frequently packaged in nucleosome-depleted cells. We suggest that by modulating the occupancy of nucleosomes histone availability may constitute a novel layer of epigenetic regulation.
Publication Title
Substantial histone reduction modulates genomewide nucleosomal occupancy and global transcriptional output.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 83 Downloadable Samples
IlluminaHiSeq2000
Description
Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: study of transcriptome during the development of MLL-AF9 AML
Publication Title
Modeling human MLL-AF9 translocated acute myeloid leukemia from single donors reveals RET as a potential therapeutic target.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 63 Downloadable Samples
- IlluminaHiSeq2000
Description
Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: study of transcriptome during the development of MLL-AF9 B-ALL
Publication Title
Modeling human MLL-AF9 translocated acute myeloid leukemia from single donors reveals RET as a potential therapeutic target.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq2000
Description
Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: Transcriptome of several AML cell lines
Publication Title
Modeling human MLL-AF9 translocated acute myeloid leukemia from single donors reveals RET as a potential therapeutic target.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: Transcriptome of normal cells (CD34+) from different donors
Publication Title
Modeling human MLL-AF9 translocated acute myeloid leukemia from single donors reveals RET as a potential therapeutic target.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaHiSeq2000
Description
Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: Transcriptome of MLL-AF9 AML pediatric patients
Publication Title
Modeling human MLL-AF9 translocated acute myeloid leukemia from single donors reveals RET as a potential therapeutic target.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The ventrolateral hypothalamic parvafox (formerly called PV1-Foxb1) nucleus is an anatomical entity of recent discovery and unknown function. With a view to gaining an insight into its putative functional role(s), we conducted a gene-microarray analysis.
Publication Title
Parvalbumin-Neurons of the Ventrolateral Hypothalamic Parvafox Nucleus Receive a Glycinergic Input: A Gene-Microarray Study.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The hst3hst4 strain (FY background) has the HST3 and HST4 genes, encoding putative NAD-dependent deacetylases that regulate histone 3 K56 acetylation, deleted. Expression profiling using Affymetrix microarrays was used to assess the change in the gene expression in this strain in comparison to wild-type under normal growth conditions.
Publication Title
Histone H3 K56 hyperacetylation perturbs replisomes and causes DNA damage.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 218 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Investigation of gene expression profiles among patients with COPD frequent exacerbations and to find gene targets as predictors of exacerbations
Publication Title
Altered gene expression in blood and sputum in COPD frequent exacerbators in the ECLIPSE cohort.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
OT-1 Transgenic CD8 T-cells were isolated from spleens of WT, PKC theta KO, and p50 cRel DKO mice. The T-cells were either cultured with non-pulsed DC (WT only and signified as "WT - UN") or with BMDCs pulsed with the OVA peptide SIINFEKL (N4) (WT, PKC theta KO, and p50 cRel DKO and signified as 'genotype - N4') at a ratio of 1:10 (DC:T-cell) for 18 hours. DCs then were depleted from the culture and RNA was made from the T-cells to measure gene expression at the early / late stage of T-cell activation
Publication Title
NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation.
Sample Metadata Fields
Specimen part
View Samples