GEO series
STAG2 mutations and 3D genome organization, chromatin loops, and polycomb signaling in glioblastoma multiforme
GSE240343
Homo sapiens
Other; Expression profiling by high throughput sequencing
20 samples
Submitted 2024/05/07
Platform GPL24676
Summary
Inactivating mutations of genes encoding the cohesin complex are common in a wide range of human cancers. STAG2 is the most commonly mutated subunit. Here we report the impact of stable correction of endogenous, naturally occurring STAG2 mutations on gene expression, 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme. Correction of mutant STAG2 significantly altered the expression of ~10% of all expressed genes. The genes most highly regulated by STAG2 (e.g. FGF7, c-KIT, MAGE tumor antigens) were virtually all upregulated in STAG2-mutant cells. Hi-C revealed that ~3% of A/B compartments switched after STAG2 correction, and confirmed prior findings that STAG2 is dispensable for maintenance of Topologically Associating Domains (TADs). The size and strength of thousands of chromatin loops were altered by STAG2 correction, a subset of which controlled the expression of adjacent genes. Loops specific to STAG2-mutant cells and tumors were very large, supporting prior findings that STAG1-containing cohesin complexes have greater loop extrusion processivity than STAG2-containing cohesin complexes, and suggesting that long loops may be a generalizable feature of STAG2-mutant cancers. Finally, STAG2-regulated chromatin loops were enriched for the H3K27me3 Polycomb epigenetic mark, revealing that inactivation of STAG2 can activate Polycomb signaling in GBM. Together these findings illuminate the landscape of STAG2-regulated genes, A/B compartments, chromatin loops, and pathways in GBM, providing important clues into the still mysterious mechanism of STAG2 tumor suppression in human cancer.
Published in
Xu W, Kim JS, Yang T et al.
· The Journal of biological chemistry 2024
· PMID 38705393
· doi:10.1016/j.jbc.2024.107341
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE240343_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 20 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1003411 and SRA study SRP454002. Searching any of these in the dataset finder brings you back here.
Study design
16 conditions, each sampled once — no replicated groups
H4 parental ×2
H4 88-1 ×2
42MGBA parental ×2
42MGBA 53-1 ×2
Read from 20 sample titles: 16 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM7696517 H4 parental replicate 1
- GSM7696518 H4 parental replicate 2
- GSM7696519 H4 88-1 replicate 1
- GSM7696520 H4 88-1 replicate 2
- GSM7696521 42MGBA parental replicate 1
- GSM7696522 42MGBA parental replicate 2
- GSM7696523 42MGBA 53-1 replicate 1
- GSM7696524 42MGBA 53-1 replicate 2
- GSM7698149 H4 parental replicate 1 [RNA-seq]
- GSM7698150 H4 parental replicate 2 [RNA-seq]
- GSM7698151 H4 parental replicate 3 [RNA-seq]
- GSM7698152 H4 88-1 replicate 1 [RNA-seq]
- GSM7698153 H4 88-1 replicate 2 [RNA-seq]
- GSM7698154 H4 88-1 replicate 3 [RNA-seq]
- GSM7698155 42MGBA parental replicate 1 [RNA-seq]
- GSM7698156 42MGBA parental replicate 2 [RNA-seq]
- GSM7698157 42MGBA parental replicate 3 [RNA-seq]
- GSM7698158 42MGBA 53-1 replicate 1 [RNA-seq]
- GSM7698159 42MGBA 53-1 replicate 2 [RNA-seq]
- GSM7698160 42MGBA 53-1 replicate 3 [RNA-seq]
Similar datasets
- GSE270126 Divergent medulloblastoma chromatin states disclose KDM2B as a selective dependency. 219 samples
- GSE305263 Integrated RNA, translation, and proteome profiling reveals midbody remnants as selectively organized signaling vesicles 42 samples
- GSE240492 Targeting axonal guidance dependencies in glioblastoma with ROBO1 CAR T cells 41 samples
- GSE238012 Integrating multisector molecular characterization into personalized peptide vaccine design for patients with newly diagnosed glioblastoma. 16 samples
- GSE307965 MiR-342 suppression of an E2F signaling network limits metastatic outgrowth of triple negative breast cancer 15 samples
- GSE300844 Deciphering the functional impact of Alzheimer’s Disease-associated variants in resting and proinflammatory immune cells 192 samples
- GSE310353 In situ multi-modal characterization of pancreatic cancer reveals tumor cell identity as a defining factor of the surrounding microenvironment 116 samples
- GSE307215 Spatiotemporal Single-Cell Profiling Reveals T Cell Clonal Dynamics and Phenotypic Plasticity in Human Graft-versus-Host Disease 104 samples
Share this dataset
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.