GEO series
H2A.Z histone variants facilitate HDACi-dependent removal of H3.3K27M mutant protein in paediatric high-grade glioma cells
GSE232283
Homo sapiens (human)
ChIP-seq / ATAC-seq (genome binding and open chromatin)
47 samples
Submitted 2024/05/01
Platform GPL24676Platform GPL11154
At a glance
ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 47 samples
- What it is
- ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
- Organism
- Homo sapiens (human)
- Samples
- 47 samples: 37 distinct titles, 5 of them repeatedGroups are read from the sample names, not from the paper. Check the list below.
- Data you can get
- A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
- Paper
- H2A.Z histone variants facilitate HDACi-dependent removal of H3.3K27M mutant protein in pediatric high-grade glioma cellsCell reports · 2024
Summary (written by the submitters)
Diffuse intrinsic pontine gliomas (DIPG) are paediatric malignant gliomas developing in the brainstem, where resection is unattainable, leaving palliative radiotherapy as the major standard of care. Patients with DIPG have dismal prognosis of 9-12 months of survival and currently there is 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).
Read the full summary ↓
H3K27M causes global epigenetic alterations (a loss of H3K27 trimethylation and an increase 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 H3.3K27M 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 re-expression of repressed genes. Certain H3K27M-dependent genes 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.
Published in
Leszczynska KB, Freitas-Huhtamäki A, Jayaprakash C et al.
· Cell reports 2024
· PMID 38306270
· doi:10.1016/j.celrep.2024.113707
This dataset
Download · which file do I need?
Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.
1 · Just have a look
Processed table
The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.
2 · Re-analyse it
Supplementary files
The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE232283_RAW.tar (it can run to tens of gigabytes).
3 · Start from the raw reads
Raw sequencing reads
The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.
What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.
Also filed as BioProject PRJNA971530 and SRA study SRP437096. Searching any of these in the dataset finder brings you back here.
Study design
37 distinct titles, 5 of them repeated
DIPGXIII, RNA-seq, DMSO, ×3
DIPGXIII, RNA-seq, 3h after SB939, ×3
DIPGXIII, RNA-seq, 16h after SB939, ×3
DIPGXIII, RNA-seq, 48h after SB939, ×3
DIPGXIII, RNA-seq, 72h after SB939, ×3
How we read this: Read from 47 sample titles: 37 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.
Samples in this study
- GSM7324880 Sample 1_SF7761, RNA-seq, DMSO
- GSM7324881 Sample 2_SF7761, RNA-seq, SB939
- GSM7324882 Sample 3_SF7761, RNA-seq, DMSO
- GSM7324883 Sample 4_SF7761, RNA-seq, SB939
- GSM7324884 Sample 5_DIPGXIII, RNA-seq, DMSO
- GSM7324885 Sample 6_DIPGXIII, RNA-seq, SB939
- GSM7324886 Sample 7_DIPGXIII, RNA-seq, DMSO
- GSM7324887 Sample 8_DIPGXIII, RNA-seq, SB939
- GSM7324888 Sample 9_SF7761, ChIP-seq H2A.Z, DMSO
- GSM7324889 Sample 10_SF7761, ChIP-seq H2A.Z, SB939
- GSM7324890 Sample 11_SF7761, ChIP-seq H2A.Z, DMSO
- GSM7324891 Sample 12_SF7761, ChIP-seq H2A.Z, SB939
- GSM7324892 Sample 13_DIPGXIII, ChIP-seq H2A.Z, DMSO
- GSM7324893 Sample 14_DIPGXIII, ChIP-seq H2A.Z, SB939
- GSM7324894 Sample 15_DIPGXIII, ChIP-seq H2A.Z, DMSO
- GSM7324895 Sample 16_DIPGXIII, ChIP-seq H2A.Z, SB939
- GSM7324896 Sample 17_SF7761, ChIP-seq H3.3, DMSO
- GSM7324897 Sample 18_SF7761, ChIP-seq H3.3, SB939
- GSM7324898 Sample 19_SF7761, ChIP-seq H3.3, DMSO
- GSM7324899 Sample 20_SF7761, ChIP-seq H3.3, SB939
- GSM7324900 Sample 21_DIPGXIII, ChIP-seq H3.3, DMSO
- GSM7324901 Sample 22_DIPGXIII, ChIP-seq H3.3, SB939
- GSM7324902 Sample 23_DIPGXIII, ChIP-seq H3.3, DMSO
- GSM7324903 Sample 24_DIPGXIII, ChIP-seq H3.3, SB939
- GSM7324904 Sample 25_SF7761, ChIP-seq H3.3K27M, DMSO
- GSM7324905 Sample 26_SF7761, ChIP-seq H3.3K27M, SB939
- GSM7324906 Sample 27_SF7761, ChIP-seq H3.3K27M, DMSO
- GSM7324907 Sample 28_SF7761, ChIP-seq H3.3K27M, SB939
- GSM7324908 Sample 29_DIPGXIII, ChIP-seq H3.3K27M, DMSO
- GSM7324909 Sample 30_DIPGXIII, ChIP-seq H3.3K27M, SB939
- GSM7324910 Sample 31_DIPGXIII, ChIP-seq H3.3K27M, DMSO
- GSM7324911 Sample 32_DIPGXIII, ChIP-seq H3.3K27M, SB939
- GSM7855167 DIPGXIII, RNA-seq, DMSO, replicate 1
- GSM7855168 DIPGXIII, RNA-seq, DMSO, replicate 2
- GSM7855169 DIPGXIII, RNA-seq, DMSO, replicate 3
- GSM7855170 DIPGXIII, RNA-seq, 3h after SB939, replicate 1
- GSM7855171 DIPGXIII, RNA-seq, 3h after SB939, replicate 2
- GSM7855172 DIPGXIII, RNA-seq, 3h after SB939, replicate 3
- GSM7855173 DIPGXIII, RNA-seq, 16h after SB939, replicate 1
- GSM7855174 DIPGXIII, RNA-seq, 16h after SB939, replicate 2
+ 7 more — browse all 47 samples with per-sample file links →
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- GSE232112 Roles of H2A.Z histone variant isoforms during enterocyte-like differentiation process (ChIP-Seq) 17 samples shares h2a, histone
- GSE252447 RING1 missense variants reveal sensitivity of DNA damage repair to H2A monoubiquitination dosage during neurogenesis [bulk RNA-seq] 15 samples shares h2a, variants
- GSE289711 Regulation of Epstein–Barr Virus latency by histone variant H2A.Z [ChIP-seq] 10 samples shares h2a, histone
- GSE250466 Oncohistone H3.3K27M-driven CREB5/ID1 Axis Mediates the Malignant Cell States of Diffuse Intrinsic Pontine Glioma (DIPG) [RNA-seq] 10 samples shares 3k27m, histone
- GSE233361 TRMT6-mediated tRNA m1A modification acts as a translational checkpoint of histone synthesis and facilitates colorectal cancer progression 18 samples shares facilitate, histone
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