GEO series

Insulator dysfunction and oncogene activation in IDH mutant gliomas

GSE70991 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 33 samples Submitted 2015/12/23 Platform GPL15520Platform GPL16791Platform GPL18573

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 33 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)
Topic: Lower-grade gliomaThis series is part of our curated briefing on it.
Samples: 33 samples: 33 samples, each with a distinct title — no replicated groupsGroups 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.

Summary (written by the submitters)

Gain-of-function IDH mutations define major clinical and prognostic classes of gliomas. Mutant IDH protein produces a novel onco-metabolite, 2-hydroxyglutarate (2-HG), that interferes with iron-dependent hydroxylase enzymes, including the TET family of 5'-methylcytosine hydroxylases. TET enzymes are critical for the dynamic regulation of DNA methylation.

Read the full summary ↓

IDH mutant gliomas thus manifest a CpG island methylator phenotype (G-CIMP), though the functional significance of this altered epigenetic state remains unclear. Here we show that IDH1 mutant gliomas exhibit hyper-methylation at CTCF binding sites, leading to reduced binding of this methylation-sensitive insulator protein. Loss of CTCF binding is associated with a loss of insulation between topological domains and aberrant gene activation. We specifically demonstrate that loss of CTCF at a domain boundary permits a constitutive enhancer to aberrantly interact with the receptor tyrosine kinase gene PDGFRA, a prominent glioma oncogene. Treatment of IDH mutant gliomaspheres with demethylating agent partially restores insulator function and reduces PDGFRA expression. Conversely, CRISPR-mediated disruption of the CTCF binding sequence in IDH wildtype gliomaspheres induces PDGFRA expression and increases proliferation. Our study suggests that IDH mutations promote gliomagenesis by disrupting chromosomal topology and allowing aberrant regulatory interactions that induce oncogene expression.

This dataset

Open GSE70991 in finder → Find more human ChIP / ATAC / CUT&Tag datasets → Lower-grade glioma landscape →

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.

Series matrix ↓

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 GSE70991_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

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.

Raw reads on ENA ↗

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 PRJNA290069. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 26700815) ↗

Study design

33 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 33 sample titles: 33 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

GSM1824797 BT142 CTCF
GSM1824798 BT142 Input
GSM1824799 GSC4 CTCF
GSM1824800 GSC4 H3K27ac
GSM1824801 GSC6 CTCF
GSM1824802 GSC6 Input
GSM1824803 AA16m CTCF
GSM1824804 AA16m Input
GSM1824805 GBM2w CTCF
GSM1824806 GBM2w H3K27ac
GSM1824807 AA15m CTCF
GSM1824808 AA15m H3K27ac
GSM1824809 AA15m Input
GSM1824810 GBM1w CTCF
GSM1824811 GBM1w H3K27ac
GSM1824812 GSC119 CTCF
GSM1824813 GSC119 H3K27ac
GSM1908568 GBM1w Input
GSM1908569 GBM2w Input
GSM1908570 GBM3w CTCF
GSM1908571 GBM3w Input
GSM1908572 GBM5w CTCF
GSM1908573 GBM5w Input
GSM1908574 GBM6w CTCF
GSM1908575 GBM6w Input
GSM1908576 GBM7w CTCF
GSM1908577 GBM7w Input
GSM1908578 AA17m CTCF
GSM1908579 AA17m Input
GSM1908580 OD18m CTCF
GSM1908581 OD18m Input
GSM1908582 AA19m CTCF
GSM1908583 AA19m Input

More Lower-grade glioma datasets

GSE308634 Transcriptional changes mediated by the HDACi panobinostat in IDH-wildtype and IDH-mutant gliomas 54 samples same disease briefing · shares idh, gliomas, mutant
GSE252245 Exploiting the therapeutic vulnerability of IDH-mutant gliomas with zotiraciclib 24 samples same disease briefing · shares idh, gliomas, mutant
GSE134120 Combination of epigenetic enzyme inhibitors, GSKJ4 and Belinostat, reveals efficacy in IDH1 mutant gliomas 16 samples same disease briefing · shares idh, gliomas, mutant
GSE241745 Single-cell transcription and chromatin accessbility profiles of IDH mutant gliomas 14 samples same disease briefing · shares idh, gliomas, mutant
GSE308631 Changes in Histone H3 acetylation in panobinostat-treated IDH-wildtype and IDH-mutant glioma cultures 28 samples same disease briefing · shares idh, mutant
GSE89567 Single cell RNA-seq analysis of IDH-mutant astrocytoma 6341 samples same disease briefing · shares idh, mutant
GSE260997 Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma III 2458 samples same disease briefing · shares idh, mutant
GSE326221 Acquired genetic and cell state changes in IDH-mutant glioma progression [snRNA-seq] 75 samples same disease briefing · shares idh, mutant

Search all human ChIP / ATAC / CUT&Tag datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.