GEO DataSets

(Submitter supplied) Sequencing of paediatric gliomas has identified two common substitution mutations (K27M and G34R) in genes encoding histone H3.3. We introduced a single-copy H3.3 G34R targeted mutation in mouse ES cells and observed gains in H3K36me3 and H3K9me3 across the genome. Altered chromatin profiles correlated with enrichment of KDM4 A/B/C, a histone lysine (K9/K36) demethylase. RNA-seq of H3.3 G34R mutant showed disrupted gene expression patterns which also correlated with KDM4 enrichment. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18480

4 Samples

Download data: BW, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL21493 GPL18480

6 Samples

Download data: BW, TXT

(Submitter supplied) Sequencing of paediatric gliomas has identified two common substitution mutations (K27M and G34R) in genes encoding histone H3.3. We introduced a single-copy H3.3 G34R targeted mutation in mouse ES cells and observed gains in H3K36me3 and H3K9me3 across the genome. Altered chromatin profiles correlated with enrichment of KDM4 A/B/C, a histone lysine (K9/K36) demethylase. RNA-seq of H3.3 G34R mutant showed disrupted gene expression patterns which also correlated with KDM4 enrichment. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21493

2 Samples

Download data: BW, TXT

(Submitter supplied) Pediatric high-grade gliomas (pHGGs) harboring the K27M mutation of H3F3A (histone H3.3) are characterized by global reduction of the repressive histone mark H3K27me3 and DNA hypomethylation. Analysis of K27M-induced changes on H3K27me3 occupancy and DNA methylation at differentially expresed genes (K27M vs. wild-type H3.3) in primary pHGG tumor samples.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

22 Samples

Download data: CEL

(Submitter supplied) Histone H3.3 glycine 34 to arginine/valine (H3.3G34R/V) mutations occur in deadly hemispheric high-grade gliomas. These tumors show exquisite regional and temporal specificity, suggesting a developmental context permissive to the effects of G34R/V mutations. Here we present the molecular landscape of G34R/V gliomas (n = 83) and show that ~50% bear activating mutations in PDGFRA, with strong selection pressure for PDGFRAMUT clones at recurrence. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing; Other; Genome binding/occupancy profiling by high throughput sequencing

4 related Platforms

80 Samples

Download data: BEDPE, BW, TXT

(Submitter supplied) We over-expressed an epigenetic regulator in a glioblastoma (GBM) primary culture from an adult patient. These GBM cells have cancer stem cell phenotypes, as they have self-renewal properties and tumor initiation potential when transplanted in immunocompromised mice. ATAC-seq was performed on cells over-expressing the epigenetic regulator and control cells expressing EGFP.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Other

Platform:

GPL16791

12 Samples

Download data: NARROWPEAK

(Submitter supplied) Mutations in the histone 3 variant H3.3 have been identified in one-third of pediatric glioblastomas (GBMs), but not in adult tumors. Here we show that H3.3 is a dynamic determinant of functional properties in adult GBM. H3.3 is repressed by mixed lineage leukemia 5 (MLL5) in self-renewing GBM cells. MLL5 is a global epigenetic repressor that orchestrates reorganization of chromatin structure by punctuating chromosomes with foci of compacted chromatin, favoring tumorigenic and self-renewing properties. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL17586

6 Samples

Download data: CEL, TXT

(Submitter supplied) Genome wide DNA methylation profiling of fourteen adult GBM primary cultures and their comparison to pediatric GBMs [GSE36278; GSE55712]

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

14 Samples

Download data: IDAT, TXT

(Submitter supplied) High-grade pediatric gliomas often contain histone H3.3 mutations, but open questions remain about oncogenic mechanisms. To address this gap, we performed ‘reciprocal gene editing’ using CRISPR-Cas9 to introduce H3.3 mutations (K27M, G34R) into H3.3-wildtype brain and glioma cells, while in parallel reverting pre-existing K27M mutations in glioma cells back to wildtype. Analyses of our reciprocally-edited cells indicate that H3.3 mutation leads to specific transcriptomic and epigenetic events, and associated cell biological changes including in xenograft assays. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

20 Samples

Download data: NARROWPEAK

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL24676 GPL11154

110 Samples

Download data: BROADPEAK, BW, NARROWPEAK, TXT

(Submitter supplied) Point mutations within the histone H3.3 are frequent in aggressive childhood brain tumours known as paediatric high-grade gliomas (pHGGs). Intriguingly, different mutations arise in discrete anatomical regions: H3.3-G34R within the forebrain and H3.3-K27M preferentially within the hindbrain. The reasons for this contrasting aetiology are unknown. By engineering human foetal neural stem cell cultures from distinct regions, we demonstrate here that cell-intrinsic regional identity provides differential responsiveness to each mutant that mirrors the origins of pHGGs. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

40 Samples

Download data: BROADPEAK, BW, NARROWPEAK, TXT

(Submitter supplied) Point mutations within the histone H3.3 are frequent in aggressive childhood brain tumours known as paediatric high-grade gliomas (pHGGs). Intriguingly, different mutations arise in discrete anatomical regions: H3.3-G34R within the forebrain and H3.3-K27M preferentially within the hindbrain. The reasons for this contrasting aetiology are unknown. By engineering human foetal neural stem cell cultures from distinct regions, we demonstrate here that cell-intrinsic regional identity provides differential responsiveness to each mutant that mirrors the origins of pHGGs. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

70 Samples

Download data: TXT

(Submitter supplied) High-throughput sequencing of numerous patient samples has identified a myriad of frequent mutations of epigenetic regulators in human cancers, including recently discovered mutations in histone-encoding genes. Lysine-to-methionine mutations such as H3K27M and H3K36M share a common mechanism of inhibiting methylation pathways at the genome-wide level to promote tumorigenesis. However, the mechanism underlying the molecular and cellular changes due to H3G34 alterations is yet to be determined. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21290

22 Samples

Download data: BW

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome variation profiling by high throughput sequencing

Platforms:

GPL17021 GPL21626

30 Samples

Download data

(Submitter supplied) Diffuse intrinsic pontine gliomas (DIPG) are devastating pediatric brain tumors for which there is no effective therapy. A lack of pre-clinical genetic models has affected efforts to develop therapies targeted to DIPG. Over 60% of DIPG patients carry a mutation in the histone H3F3A gene (H3.3K27M) that is often accompanied by a mutation in the TP53 gene. Here we created a genetic model in which H3.3K27M is expressed under the mouse Fabp7 promoter. more...

Organism:

Mus musculus

Type:

Genome variation profiling by high throughput sequencing

Platforms:

GPL17021 GPL21626

16 Samples

Download data: VCF

(Submitter supplied) Diffuse intrinsic pontine gliomas (DIPG) are devastating pediatric brain tumors for which there is no effective therapy. A lack of pre-clinical genetic models has affected efforts to develop therapies targeted to DIPG. Over 60% of DIPG patients carry a mutation in the histone H3F3A gene (H3.3K27M) that is often accompanied by a mutation in the TP53 gene. Here we created a genetic model in which H3.3K27M is expressed under the mouse Fabp7 promoter. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL17021 GPL21626

14 Samples

Download data: TXT

(Submitter supplied) Relative mRNA abundance of all S. cerevisiae genes was measured in various mutants, compared to wild-type Keywords: quadruplicate mutant:WT analysis, with dye-swapping

Organism:

Saccharomyces cerevisiae

Type:

Expression profiling by array

Platform:

GPL3819

8 Samples

Download data: GPR

(Submitter supplied) We identified that RACK7 recognizes the histone H3.3G34R mutaion in vitro and in vivo. In order to explore the function of RACK7 and H3.3G34R mutaion, we used three pediatric glioblastomas(pGBM) cell lines. SJ-HGGx6c(R6) and SJ-HGGx42c(R42) have heterozygous G34R mutation, while SJ-HGGx39c(WT39) has wildtype H3F3A, which encodes H3.3. We next corrected H3.3G34R in R6 and R42 cells to wildtype H3.3 by CRISPR/Cas9 mediated knock-in, and knocked out RACK7 in R6 and R42 cells by CRISPR/Cas9. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20795

12 Samples

Download data: TXT

(Submitter supplied) We identified that RACK7 recognizes the histone H3.3G34R mutaion in vitro. In order to determine the interaction between RACK7 and H3.3G34R mutaion in cells, we used three pediatric glioblastoma (pGBM) cell lines. SJ-HGGx6c(R6) and SJ-HGGx42c(R42) have heterozygous G34R mutation, while SJ-HGGx39c(WT39) has wildtype H3F3A, which encodes H3.3, and we also corrected H3.3G34R in R6 and R42 cells to wildtype H3.3 by CRISPR/Cas9 mediated knock-in. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL20795

16 Samples

Download data: BED

(Submitter supplied) Self-renewal is a crucial property of glioblastoma cells and is enabled by the choreographed function of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could represent an important step toward developing new and effective treatments for this universally lethal cancer. Here we uncover a targetable epigenetic axis of self-renewal mediated by the histone variant macroH2A2.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

4 Samples

Download data: BED