GEO DataSets

(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; Homo sapiens

Type:

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

Platforms:

GPL17021 GPL16791

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:

GPL13112 GPL11154

13 Samples

Download data: BW, TXT

(Submitter supplied) A methionine substitution at lysine 27 on histone H3 variants (H3K27M) characterizes ~80% of diffuse intrinsic pontine gliomas (DIPG) and inhibits PRC2 in a dominant negative fashion. Yet, the mechanisms for this inhibition and abnormal epigenomic landscape have not been resolved. Using quantitative proteomics, we discovered that robust PRC2 inhibition requires levels of H3K27M greatly exceeding those of PRC2, seen in DIPG. more...

Organism:

Homo sapiens

Type:

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

Platform:

GPL18573

64 Samples

Download data: BW

(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

Platform:

GPL16791

30 Samples

Download data: BED, BIGWIG, TXT

(Submitter supplied) Histone H3 lysine 27 to methionine mutations (H3K27M) resulting in aberrant chromatin regulation are frequently observed in Diffuse Intrinsic Pontine Glioma (DIPG), a pediatric brain tumor with no cure. We conducted a CRISPR screen to determine if various chromatin regulators might be targeted to treat DIPG. Excitingly, this genetic screen reveals that co-targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDACs) results in an enhanced growth suppressive effect in patient DIPG cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: TXT

(Submitter supplied) Histone H3 lysine 27 to methionine mutations (H3K27M) resulting in aberrant chromatin regulation are frequently observed in Diffuse Intrinsic Pontine Glioma (DIPG), a pediatric brain tumor with no cure. We conducted a CRISPR screen to determine if various chromatin regulators might be targeted to treat DIPG. Excitingly, this genetic screen reveals that co-targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDACs) results in an enhanced growth suppressive effect in patient DIPG cells. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

18 Samples

Download data: BED, BIGWIG

(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:

Mus musculus; Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL13112 GPL11154

43 Samples

Download data: BW

(Submitter supplied) Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brain tumor with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone 3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using either bromodomain inhibition or CDK7 blockade. We observe that targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition and that DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade. more...

Organism:

Homo sapiens

Type:

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

Platforms:

GPL18573 GPL20301

26 Samples

Download data: BW, TXT

(Submitter supplied) The discovery of H3K27M mutations in pediatric gliomas marked a new chapter in cancer epigenetics. Numerous studies have investigated the effect of this mutation on H3K27 trimethylation, but only recently have we started to realize its additional effects on the epigenome. Here, we use isogenic glioma H3K27M(+/-) cell lines to investigate H3K27 methylation and its interaction with H3K36 and H3K9 modifications. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

14 Samples

Download data: BW

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

Organism:

Homo sapiens

Type:

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

5 related Platforms

135 Samples

Download data: BW, TDF

(Submitter supplied) The discovery of H3K27M mutations in pediatric gliomas marked a new chapter in cancer epigenetics. Numerous studies have investigated the effect of this mutation on H3K27 trimethylation, but only recently have we started to realize its additional effects on the epigenome. Here, we use isogenic glioma H3K27M(+/-) cell lines to investigate H3K27 methylation and its interaction with H3K36 and H3K9 modifications. more...

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platforms:

GPL16791 GPL20795

7 Samples

Download data: TDF

(Submitter supplied) The discovery of H3K27M mutations in pediatric gliomas marked a new chapter in cancer epigenetics. Numerous studies have investigated the effect of this mutation on H3K27 trimethylation, but only recently have we started to realize its additional effects on the epigenome. Here, we use isogenic glioma H3K27M(+/-) cell lines to investigate H3K27 methylation and its interaction with H3K36 and H3K9 modifications. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

4 related Platforms

114 Samples

Download data: BW

(Submitter supplied) Epigenetic alterations are recurrently observed in cancer and are the subject of active therapeutic investigations. Midline high-grade gliomas (HGGs) are deadly brain tumors characterized by lysine-to-methionine substitutions at position 27 in histone 3 (H3) variants (denoted H3K27M), which are core components of the nucleosome. H3K27M, the first event in midline HGG development, results in a drastic loss of the repressive histone mark H3K27 tri-methylation (H3K27me3), and a notable increase in H3K27 acetylation (H3K27ac), a mark associated with active chromatin and cellular identity. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

4 related Platforms

22 Samples

Download data: TXT

(Submitter supplied) Epigenetic alterations are recurrently observed in cancer and are the subject of active therapeutic investigations. Midline high-grade gliomas (HGGs) are deadly brain tumors characterized by lysine-to-methionine substitutions at position 27 in histone 3 (H3) variants (denoted H3K27M), which are core components of the nucleosome. H3K27M, the first event in midline HGG development, results in a drastic loss of the repressive histone mark H3K27 tri-methylation (H3K27me3), and a notable increase in H3K27 acetylation (H3K27ac), a mark associated with active chromatin and cellular identity. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL20301

80 Samples

Download data: BED

(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

4 related Platforms

210 Samples

Download data: BED, NARROWPEAK

(Submitter supplied) Epigenetic alterations are recurrently observed in cancer and are the subject of active therapeutic investigations. Midline high-grade gliomas (HGGs) are deadly brain tumors characterized by lysine-to-methionine substitutions at position 27 in histone 3 (H3) variants (denoted H3K27M), which are core components of the nucleosome. H3K27M, the first event in midline HGG development, results in a drastic loss of the repressive histone mark H3K27 tri-methylation (H3K27me3), and a notable increase in H3K27 acetylation (H3K27ac), a mark associated with active chromatin and cellular identity. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: NARROWPEAK

(Submitter supplied) Epigenetic alterations are recurrently observed in cancer and are the subject of active therapeutic investigations. Midline high-grade gliomas (HGGs) are deadly brain tumors characterized by lysine-to-methionine substitutions at position 27 in histone 3 (H3) variants (denoted H3K27M), which are core components of the nucleosome. H3K27M, the first event in midline HGG development, results in a drastic loss of the repressive histone mark H3K27 tri-methylation (H3K27me3), and a notable increase in H3K27 acetylation (H3K27ac), a mark associated with active chromatin and cellular identity. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL16791 GPL20301 GPL11154

96 Samples

Download data: TXT

(Submitter supplied) Diffuse intrinsic pontine glioma (DIPG) is a fatal malignancy of the childhood pons characterized by a unique lysine-to-methionine substitution in histone-3 at lysine 27 (H3K27M). We show here that the specific Polycomb targets disrupted by H3K27M and resultant oncogenic state is dependent on both the variant of histone-3 and the cell- context in which the mutation occurs. Through primary DIPG tumor characterization and isogenic expression, we show that the same H3K27M mutation displays distinct modes of oncogenic reprogramming and establishes distinct enhancer architecture depending on whether it occurs in genes encoding H3.3 or H3.1. more...

Organism:

Homo sapiens

Type:

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

Platforms:

GPL18573 GPL11154 GPL20795

155 Samples

Download data: BW, CSV, VCF, XLSX