GEO DataSets

(Submitter supplied) Using the RCAS/tv-a system, we induced murine brainstem gliomas (PDGF-B; p53 loss using RCAS-Cre with and without H3.3K27M) in Nestin tv-a; p53 floxed mice

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL9185

6 Samples

Download data: XLSX

(Submitter supplied) Expression of histone H3.3K27M mutant proteins in diffuse intrinsic pontine glioma (DIPG) results in a global reduction of tri-methylation of H3K27 (H3K27me3), and paradoxically, H3K27me3 peaks remain at hundreds of genomic loci, a dichotomous change that lacks mechanistic insights. Here we show that the PRC2 complex is sequestered at poised enhancers, but not at active promoters with high levels of H3.3K27M proteins, thereby contributing to the global reduction of H3K27me3. more...

Organism:

Homo sapiens; Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL11154 GPL13112

43 Samples

Download data: BW

(Submitter supplied) Diffuse intrinsic pontine glioma (DIPG) is a rare and fatal pediatric brain cancer without cure. DIPG has high percentage histone mutation at K27M on histone H3 locus, which is believed to be one of the drivers of the tumorigenesis. Dysregulation of G1/S cell cycle checkpoint is more enriched in the H3.3K27M mutant subgroup. In this study, we reported that palbociclib (PD0332991), a specific and cytostatic inhibitor of CDK4/6, effectively suppresses the growth of DIPG cells in vitro and in vivo. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20795

4 Samples

Download data: FPKM_TRACKING

(Submitter supplied) Recent studies have identified a Lys 27-to-methionine (K27M) mutation at one allele of H3F3A, one of the two genes encoding histone H3 variant H3.3, in 60% of high-grade pediatric glioma cases. The median survival of this group of patients after diagnosis is ∼1 yr. Here we show that the levels of H3K27 di- and trimethylation (H3K27me2 and H3K27me3) are reduced globally in H3.3K27M patient samples due to the expression of the H3.3K27M mutant allele. more...

Organism:

Homo sapiens

Type:

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

Platform:

GPL11154

16 Samples

Download data: BED, BW, TXT

(Submitter supplied) Background: The histone variant H3.3 K27M mutation is a defining characteristic of diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG). This histone mutation is responsible for major alterations to histone H3 post-translational modification (PTMs) and subsequent aberrant gene expression. However, much less is known about the effect this mutation has on chromatin structure and function, including open versus closed chromatin regions as well as their transcriptomic consequences. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

8 Samples

Download data: BED

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

Organism:

Homo sapiens; Mus musculus

Type:

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

Platforms:

GPL16791 GPL17021

38 Samples

Download data: BED, BW

(Submitter supplied) Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive brain tumour that is located in the pons and primarily affects children. Whole-exome sequencing studies have identified recurrent driver mutations in H3F3A and HIST1H3B, leading to the expression of histone H3 in which lysine 27 is substituted with methionine (H3K27M) in nearly 80% of DIPGs. H3K27M inhibits Polycomb Repressive Complex 2 (PRC2) activity by binding to its catalytic subunit EZH2 and although DIPGs with H3K27M mutation show global loss of H3 with trimethylated lysine 27 (H3K27me3), several genomic loci are still H3K27me3 positive. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

8 Samples

Download data: BW

(Submitter supplied) Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive brain tumour that is located in the pons and primarily affects children. Whole-exome sequencing studies have identified recurrent driver mutations in H3F3A and HIST1H3B, leading to the expression of histone H3 in which lysine 27 is substituted with methionine (H3K27M) in nearly 80% of DIPGs. H3K27M has been shown to inhibit Polycomb Repressive Complex 2 (PRC2) activity by binding to its catalytic subunit EZH2, and although DIPGs with H3K27M mutation show global loss of H3 with trimethylated lysine 27 (H3K27me3), several genes retain H3K27me3. more...

Organism:

Homo sapiens; Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL11154 GPL13112

13 Samples

Download data: BW, TXT

(Submitter supplied) Lysine27Methionine mutations (K27M) in the histone H3 (H3.3 and H3.1) are highly prevalent in pediatric high-grade gliomas (HGG). This study found H3.3K27M caused the upregulation of multiple cancer/testis (CT) antigens, include IL13RA2 and VCX family proteins. Overexpression of VCX3A/B stimulates the expression of genes involved in immune response.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

16 Samples

Download data: TXT

(Submitter supplied) Xenografts from human pediatric brainstem gliomas bearing K27M in H3F3A were transduced with non silencing or H3F3A shRNA to assess the impact of the K27M on tumor growth, gene expression and epigenetics

Organism:

Homo sapiens

Type:

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

Platforms:

GPL16791 GPL20301

130 Samples

Download data: BED, BW, NARROWPEAK

(Submitter supplied) xenografts from human pediatric brainstem gliomas bearing K27M in H3F3A were transduced with non silencing or H3F3A shRNA to assess the impact of the K27M on tumor growth, gene expression and epigenetics

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL16791 GPL20301

50 Samples

Download data: TXT

(Submitter supplied) Xenografts from human pediatric brainstem gliomas bearing K27M in H3F3A were transduced with non silencing or H3F3A shRNA to assess the impact of the K27M on tumor growth, gene expression and epigenetics

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL16791 GPL20301

80 Samples

Download data: BED, BW, NARROWPEAK

(Submitter supplied) Diffuse midline glioma (DMG) is a type of lethal brain tumor that develops mainly in children. The majority of DMG harbor the K27M mutation in histone H3. Oligodendrocyte progenitor cells (OPCs) in the brainstem are candidate cells-of-origin for DMG, yet there is no genetically engineered mouse model of DMG initiated in OPCs. Here, we used the RCAS/Tv-a avian retroviral system to generate DMG in Olig2-expressing progenitors and Nestin-expressing progenitors in the neonatal mouse brainstem. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

10 Samples

Download data: XLSX

(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) Diffuse intrinsic pontine gliomas (DIPG) are characterized by a heterozygous lysine-to-methionine mutation of histone H3 (H3K27M) that potently reduces Polycomb Repressive Complex 2 (PRC2) methylation of wild-type histone H3K27 (H3K27wt). The role of H3K27M and reduced H3K27wt methylation in DIPG pathogenesis has yet to be determined. Here, we have performed epigenomic profiling of patient-derived H3K27M mutant DIPG cells and demonstrate that H3K27M resides in nucleosomes with H3K27wt acetylation (H3K27ac), and H3K27M-H3K27ac containing nucleosomes co-localize with bromodomain proteins at actively transcribed genes and that PRC2 is excluded from H3K27M occupied regions. more...

Organism:

Homo sapiens

Type:

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

Platform:

GPL18573

100 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 binding/occupancy profiling by high throughput sequencing

Platforms:

GPL21103 GPL17021

100 Samples

Download data: BED, BW, NARROWPEAK

(Submitter supplied) A mouse knock-in model engineered for Cre recombinase-activated expression of the endogenous mouse H3f3a allele generating an epitope-tagged H3.3 equipped with or without a K27M mutation to investigate H3.3 K27M effects on brain cell and tumor growth, gene expression and epigenetics.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL17021 GPL21103

41 Samples

Download data: TXT

(Submitter supplied) A mouse knock-in model engineered for Cre recombinase-activated expression of the endogenous mouse H3f3a allele generating an epitope-tagged H3.3 equipped with or without a K27M mutation to investigate H3.3 K27M effects on brain cell and tumor growth, gene expression and epigenetics.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17021

59 Samples

Download data: BED, BW, NARROWPEAK