Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA261535 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1582160_1.fastq.gz | Fastqsanger.gz | |||
| SRR1582160_2.fastq.gz | Fastqsanger.gz | |||
| SRR1582161_1.fastq.gz | Fastqsanger.gz | |||
| SRR1582161_2.fastq.gz | Fastqsanger.gz | |||
| SRR1582162_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description: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. Remarkably, we also observed that H3K27me3 and Ezh2 (the catalytic subunit of H3K27 methyltransferase) at chromatin are dramatically increased locally at hundreds of gene loci in H3.3K27M patient cells. Moreover, the gain of H3K27me3 and Ezh2 at gene promoters alters the expression of genes that are associated with various cancer pathways. These results indicate that H3.3K27M mutation reprograms epigenetic landscape and gene expression, which may drive tumorigenesis. We performed chromatin-immunoprecipitation of H3K27me3, H3K4me3, and EZH2 in SF7761 and NSC cell lines. And do RNA-seq in SF7761, SF8828 and NSC cell lines. SF7761 and SF8628 cell lines from patients harboring the histone H3.3 K27M mutation were obtained from Hashizume et al. (2012). NSCs (N7800-100) were purchased from Invitrogen and cultured and maintained in NSC medium (A10509-01, StemPro NSC SFM, Invitrogen).
2014-09-20 | E-GEOD-61586 | biostudies-arrayexpress
Project description: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. Remarkably, we also observed that H3K27me3 and Ezh2 (the catalytic subunit of H3K27 methyltransferase) at chromatin are dramatically increased locally at hundreds of gene loci in H3.3K27M patient cells. Moreover, the gain of H3K27me3 and Ezh2 at gene promoters alters the expression of genes that are associated with various cancer pathways. These results indicate that H3.3K27M mutation reprograms epigenetic landscape and gene expression, which may drive tumorigenesis.
2014-09-20 | GSE61586 | GEO
Project description:Histone H3.1/3.2K27M and H3.3K27M mutation are driver mutations frequently identified in diffuse midline glioma (DMG). However, the precise mechanism by which H3K27M mediates tumorigenesis remains incompletely understood. By carrying out bait Protein-Protein Interaction followed by genome-wide screening (bPPI-seq) in H3.3WT and H3.3K27M mouse NSC models, we identified a novel histone reader CBFA2T2, which recognizes non-mutated or un-modified histone H3K27. Importantly, CBFA2T2 binding to H3K27, mediated by the NHR2 domain, is abrogated by the H3K27M oncogenic mutation. In H3.3 wildtype cells, CBFA2T2 represses transcription of genes involved in carbon metabolism and TCA cycle through its binding to H3K27. This alters the α-KG/Succinate (alpha-ketoglutarate/ Succinate) ratio and indirectly impacts H3K27me3 level, possibly through affecting the H3K27me3 demethylases. CBFA2T2 does not bind the H3.3K27M decorated chromatin in vivo, thus the K to M mutation, partially compromises the CBFA2T2 repressive function. However, over-expressing CBFA2T2 rescues the low H3K27me3 level in H3.3K27M mNSC and H3.3K27M DIPG cells, thus suppressing the H3.3K27M tumor growth. Our findings suggest a new mechanism, which may contribute to the low H3K27me3 level observed in the H3K27M cells, and provide a new strategy for H3K27M therapy through manipulation of CBFA2T2.
2026-04-22 | GSE277513 | GEO
Project description:Histone H3.1/3.2K27M and H3.3K27M mutation are driver mutations frequently identified in diffuse midline glioma (DMG). However, the precise mechanism by which H3K27M mediates tumorigenesis remains incompletely understood. By carrying out bait Protein-Protein Interaction followed by genome-wide screening (bPPI-seq) in H3.3WT and H3.3K27M mouse NSC models, we identified a novel histone reader CBFA2T2, which recognizes non-mutated or un-modified histone H3K27. Importantly, CBFA2T2 binding to H3K27, mediated by the NHR2 domain, is abrogated by the H3K27M oncogenic mutation. In H3.3 wildtype cells, CBFA2T2 represses transcription of genes involved in carbon metabolism and TCA cycle through its binding to H3K27. This alters the α-KG/Succinate (alpha-ketoglutarate/ Succinate) ratio and indirectly impacts H3K27me3 level, possibly through affecting the H3K27me3 demethylases. CBFA2T2 does not bind the H3.3K27M decorated chromatin in vivo, thus the K to M mutation, partially compromises the CBFA2T2 repressive function. However, over-expressing CBFA2T2 rescues the low H3K27me3 level in H3.3K27M mNSC and H3.3K27M DIPG cells, thus suppressing the H3.3K27M tumor growth. Our findings suggest a new mechanism, which may contribute to the low H3K27me3 level observed in the H3K27M cells, and provide a new strategy for H3K27M therapy through manipulation of CBFA2T2.
2026-04-22 | GSE277547 | GEO
Project description:Histone H3.1/3.2K27M and H3.3K27M mutation are driver mutations frequently identified in diffuse midline glioma (DMG). However, the precise mechanism by which H3K27M mediates tumorigenesis remains incompletely understood. By carrying out bait Protein-Protein Interaction followed by genome-wide screening (bPPI-seq) in H3.3WT and H3.3K27M mouse NSC models, we identified a novel histone reader CBFA2T2, which recognizes non-mutated or un-modified histone H3K27. Importantly, CBFA2T2 binding to H3K27, mediated by the NHR2 domain, is abrogated by the H3K27M oncogenic mutation. In H3.3 wildtype cells, CBFA2T2 represses transcription of genes involved in carbon metabolism and TCA cycle through its binding to H3K27. This alters the α-KG/Succinate (alpha-ketoglutarate/ Succinate) ratio and indirectly impacts H3K27me3 level, possibly through affecting the H3K27me3 demethylases. CBFA2T2 does not bind the H3.3K27M decorated chromatin in vivo, thus the K to M mutation, partially compromises the CBFA2T2 repressive function. However, over-expressing CBFA2T2 rescues the low H3K27me3 level in H3.3K27M mNSC and H3.3K27M DIPG cells, thus suppressing the H3.3K27M tumor growth. Our findings suggest a new mechanism, which may contribute to the low H3K27me3 level observed in the H3K27M cells, and provide a new strategy for H3K27M therapy through manipulation of CBFA2T2.
2026-04-22 | GSE277514 | GEO
Project description:The regulation of gene expression is controlled in part by post-translational modifications to histone proteins. Methylation at histone H3, lysine 27 (H3K27), which is catalyzed by Polycomb repressive complex 2 (PRC2), is associated with silenced chromatin. Previous studies have identified dysregulation of H3K27 methylation in pediatric diffuse intrinsic pontine gliomas (DIPGs), the majority of which feature mutation of lysine 27 to methionine. This “oncohistone” potently inhibits PRC2 activity and leads to a global reduction in H3K27 methylation. Similar to DIPG, posterior fossa type A (PFA) ependymomas also show low levels of H3K27 methylation. Although PFAs do not possess the H3K27M oncohistone mutation, they do show increased expression of Cxorf67. Interestingly, Cxorf67 contains a C-terminal sequence that resembles the sequence surrounding H3K27, and we find that this portion of Cxorf67 inhibits PRC2 activity to an even greater extent than the H3K27M oncohistone. Thus, we suggest re-naming Cxorf67 as EZHIP (Enhancer of Zeste Homologs Inhibitory Protein). Furthermore, when expressed in 293T cells, Cxorf67 interacts with several members of PRC2 and induces changes in H3K27 methylation patterns that mirror the changes in H3K27 methylation induced by expression of H3K27M. We propose that PFAs have dysregulated H3K27 methylation by a mechanism that involves inhibition of PRC2 by Cxorf67, which could drive tumorigenesis.
2019-04-09 | PXD013390 | Pride
Project description:Diffuse midline glioma (DMG) is a lethal pediatric brain cancer with limited treatment options. We developed a human brainstem organoid model to study H3.3K27M-driven DMG, enabling formation of patient-like tumors with molecular heterogeneity. To characterize the resulting tumor we performed DNA methylation and compared the generated tumor with methylation data from DMG, pGBM and PFA ependymoma patients.
2025-09-20 | E-MTAB-15559 | biostudies-arrayexpress
Project description:Diffuse intrinsic pontine gliomas (DIPG) are a deadly paediatric brain tumours, non-resectable due to brainstem localisation and diffusive growth. Patients with DIPG have a dismal prognosis of 9-12 months of survival with no effective therapy. Over 80% of DIPGs harbour a mutation in histone 3 (H3.3 or H3.1) resulting in a lysine to methionine substitution (H3K27M). H3K27M causes global epigenetic alterations (a loss of H3K27 trimethylation and an increase in H3K27 acetylation) resulting in aberrant gene expression. To date, no therapeutic strategy exists to suppress the levels of oncogenic H3K27M.
We show that pan-HDAC inhibitors (HDACi) lead to the temporary but significant reduction in the H3.33K27M protein (up to 80%) in multiple glioma cell lines expressing the H3.3K27M histone variant, without changes in the H3F3A mRNA expression. The H3.3K27M occupancy at the chromatin is greatly reduced upon HDACi (SB939) treatment, as shown by ChIPseq analysis. H3.3K27M loss is most striking at SB939-upregulated genes suggesting the role in repression of these genes. In addition, genes previously reported as H3K27M-dependent become downregulated in response to SB939 treatment. We discover that the SB939-mediated loss of H3.3K27M is partially blocked by a lysosomal inhibitor, chloroquine. Moreover, the loss of H3.3K27M is facilitated by co-occurrence of H2A.Z, as evidenced by the knock-down of H2A.Z histone isoforms. ChIPseq analysis confirms the occupancy of H3.3K27M and H2A.Z at the same SB939-inducible genes.
Altogether, we provide new insight into disease-specific mechanism of HDAC inhibition and demonstrate pharmacological modulation of the oncogenic H3.3K27M protein levels. These findings open a new possibility to directly target the H3.3K27M oncohistone, which may be exploited in future therapies.
2023-10-05 | MSV000093052 | MassIVE
Project description:Histone H3.3K27M mutation activates multiple cancer/testis antigens
| PRJNA399160 | ENA
Project description:Substitution of lysine 27 with methionine in histone H3.3 is a recently discovered driver mutation of pediatric high-grade gliomas. Tumor cells carrying the mutation show a dramatic decrease in H3K27me3 levels due to physical inhibition of PRC2 methyltransferase activity. Here we use a C. elegans model to quantify the antagonistic effects of the H3.3K27M oncohistone on H3K27 trimethylation genome wide. We demonstrate that PRC2 is locally both simulated by H3K27me3 and inhibited by the oncohistone in a concentration-dependent manner.
2019-04-26 | GSE117531 | GEO