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GSE37595
Homo sapiens
1 Downloadable Sample
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
T-bet is pivotal for initiation and perpetuation of Th1 immunity. Identification of novel T-bet regulated genes is crucial for further understanding the biology of this transcription factor.
Publication Title
IL-36γ/IL-1F9, an innate T-bet target in myeloid cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Relationship between gene body DNA methylation and intragenic H3K9me3 and H3K36me3 chromatin marks.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This is one of expressional parts of the study. These data were correlated to epigenetic marks and CG density of genes in analyzed cells. The whole study has a following summary: To elucidate possible roles of DNA methylation and chromatin marks in transcription, we performed epigenetic profiling of chromosome 19 in human bronchial epithelial cells (HBEC) and in the colorectal cancer cell line HCT116 as well as its counterpart with double knockout of DNMT1 and DNMT3B (HCT116-DKO). We found that H3K9me3 forms intragenic chromatin blocks along genes with low CpG density in the gene body. Analysis of H3K36me3 profiles indicated that this mark associates either with active genes with low CpG density and H3K9me3 in the gene body or with active genes with high CpG density and DNA hypermethylation in the gene body. In HCT116 cells with double knockout of DNMT1 and DNMT3B, transcription of genes with low CpG density in the gene body was highly elevated and associated with promoter DNA demethylation and rearrangement of H3K9me3 and H3K36me3 occupation. Our finding suggests that similar to DNA methylation, H3K9me3 may play a role in intragenic gene regulation. Further, we observed that a combination of low CpG density in gene bodies together with H3K9me3 and H3K36me3 marking is a specific epigenetic feature of zinc finger (ZNF) genes, which comprise 90% of all genes carrying both histone marks on chromosome 19. For high CpG density genes, transcription and H3K36me3 occupancy were not changed in condition of partial or intensive loss of DNA methylation in gene bodies in the HCT116-DKO cell line. siRNA experiments with SETD2 knockdown in both HBEC and HCT116-DKO cell lines failed to reduce DNA methylation in gene bodies under conditions of H3K36me3 depletion. Our study suggests that the H3K36me3 and DNA methylation marks in gene bodies are established independently from each other and points to similar functional roles of intragenic DNA methylation and intragenic H3K9me3 for CpG-rich and CpG-poor genes, respectively.
Publication Title
Relationship between gene body DNA methylation and intragenic H3K9me3 and H3K36me3 chromatin marks.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
Illumina HiSeq 2500
Description
Cell fate specification is accompanied by global changes in gene expression from patterns of maintaining stem/progenitor cells to patterns for supporting differentiation. To ensure a proper transition, it is conceivable that genes important for differentiation are kept silent in stem/progenitor cells yet can be readily activated. RNA polymerase II (Pol II) pausing and bivalent chromatin marks are two paradigms that are suited for establishing such a poised state of gene expression, however, their contributions to gene regulation in development are not well understood. Here, using neural progenitor cells (NPCs) and their daughter neurons co-purified from the embryonic mouse cerebral cortex, we characterized Pol II pausing and H3K4me3/H3K27me3 marks in this in vivo setting of neurogenesis. We show that genes paused in NPCs or neurons are well correlated with their respective cell type-specific functions, but pausing and pause release did not predict gene activation. Bivalent chromatin marks, on the other hand, poised the marked genes in NPCs for activation in neurons. Interestingly, our data also revealed a positive correlation between H3K27me3 and paused Pol II. This study thus reveals cell-type specific Pol II pausing and gene activation-associated bivalency during mammalian neuronal differentiation. Overall design: Transcriptome analyses in neural progenitor cells (NPCs) and their daughter neurons, and their relationship with RNA polymerase II pausing and histone bivalent mark
Publication Title
Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The number of long-term survivors of high-risk neuroblastoma remains discouraging, with 10-year survival as low as 20%, despite decades of considerable international efforts to improve outcome. Major obstacles remain and include managing resistance to induction therapy, which causes tumor progression and early death in high-risk patients, and managing chemotherapy-resistant relapses, which can occur years after the initial diagnosis. Identifying and validating novel therapeutic targets is essential to improve treatment. Delineating and deciphering specific functions of single histone deacetylases in neuroblastoma may support development of targeted acetylome-modifying therapeutics for patients with molecularly defined high-risk neuroblastoma profiles. We show here that HDAC11 depletion in MYCN-driven neuroblastoma cell lines strongly induces cell death, mostly mediated by apoptotic programs. Genes necessary for mitotic cell cycle progression and cell division were most prominently enriched in at least two of three time points in whole-genome expression data combined from two cell systems, and all nine genes in these functional categories were strongly repressed, including CENPA, KIF14, KIF23 and RACGAP1. Enforced expression of one selected candidate, RACGAP1, partially rescued the induction of apoptosis caused by HDAC11 depletion. High-level expression of all nine genes in primary neuroblastomas signicantly correlated with unfavorable overall and event-free survival in patients, suggesting a role in mediating the more aggressive biological and clinical phenotype of these tumors. Our study identied a group of cell cycle-promoting genes regulated by HDAC11, being both predictors of unfavorable patient outcome and essential for tumor cell viability. The data indicates a signicant role of HDAC11 for mitotic cell cycle progression and survival of MYCN-amplified neuroblastoma cells, and suggests that HDAC11 could be a valuable drug target.
Publication Title
Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 20 Downloadable Samples
- IlluminaHiSeq2500
Description
Melanoma genomes are often characterized by large numbers of sunlight-induced mutations. However, epigenetic alterations, in the form of aberrant DNA methylation patterns, are also abundant. Using MIRA-seq, we have carried out a comprehensive characterization of the DNA methylome in a series of metastatic melanoma samples and catalogued the methylation changes relative to normal melanocytes, the presumed cells of origin for these tumors. Individual melanoma tumors contained up to several thousand hypermethylated regions. We discovered 179 tumor-specific methylation peaks that were present in all (27/27) melanomas and may lend themselves as effective disease biomarkers, and 3124 methylation peaks were present in >40% of the tumors. We specifically examined the relationship between presence of the Polycomb mark, H3K27me3 in melanocytes and tumor-specific DNA methylation in melanoma. We found that 150 of the approximately 1,200 tumor-associated methylation peaks near transcription start sites (TSS) were H3K27me3-marked in melanocytes. Notably, DNA methylation in melanoma was specific for distinct H3K27me3 peaks rather than for H3K27me3-enriched regions with broad genomic coverage. Yet, there were also numerous H3K27me3 peak-associated TSS regions that were completely resistant to DNA methylation in tumors. Furthermore, a rather large group of genes became methylated in melanoma but lacked H3K27me3 in melanocytes. There was no relationship between presence of BRAF V600 mutations and the number of methylation peaks in individual tumors. Gene expression analysis showed a strong signature of upregulated immune response genes in melanomas presumably as a result of lymphocyte infiltration. Genes down-regulated in tumors were enriched for melanocyte differentiation and pigmentation factors. Overall, there was limited correlation between tumor-associated DNA methylation changes and changes in gene expression although distinct melanocyte differentiation genes including KIT, PAX3 and SOX10 became methylated and downregulated in melanoma. Overall design: Genome-wide gene expression analysis of 17 melanomas and 3 melanocyte samples
Publication Title
The DNA methylation landscape of human melanoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly due to the technical challenge of analyzing its rare neoplastic L&H cells, which are dispersed in an abundant non-neoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected lymphocytic and histiocytic (L&H) lymphoma cells in comparison to normal and other malignant B cells, which indicates a relationship of L&H cells to and/or origin from germinal center B cells at transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell-rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype and deregulation of many apoptosis-regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive NF-B activity and aberrant ERK signaling. Thus, these findings shed new light on the nature of L&H cells, revealed several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies.
Publication Title
Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- (imblegenhumandnamethylation3x720kcpgislandplusrefseqpromoterarray[100718hg18cpgrefseqprommedip), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Loss of the polycomb mark from bivalent promoters leads to activation of cancer-promoting genes in colorectal tumors.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Analysis of expression changes between colon tumors (Duke's stage II) and matching colon mucosa tissues using Affymetrix GeneChip Human Gene 2.0 ST arrays.
Publication Title
Loss of the polycomb mark from bivalent promoters leads to activation of cancer-promoting genes in colorectal tumors.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Chromosome-wide analysis of parental allele-specific chromatin and DNA methylation.
Sample Metadata Fields
Specimen part
View Samples