Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The effect of STAG2 loss in Ewing sarcoma [HiChIP]

ABSTRACT: Ewing sarcoma is an aggressive malignancy characterized by oncogenic rearrangements of the EWS gene with an ETS-family transcription factor, most commonly FLI. Recent comprehensive next-generation sequencing efforts have revealed few other highly recurrent mutations in this disease apart from loss-of-function mutations in STAG2 which occur in 15-20% of tumors. STAG2 is a member of the cohesin complex, which regulates sister chromatid alignment during mitosis and epigenetic regulation of gene expression. While some studies suggest that loss of STAG2 is associated with the development of aneuploidy, this is not the case in Ewing sarcoma. To investigate whether STAG2 loss affects epigenetic regulation of gene expression in Ewing sarcoma, we developed isogenic Ewing sarcoma cell lines with STAG2 knockout. We found that Ewing sarcoma cells engineered for loss of STAG2 maintain an intact cohesion complex that alternately incorporates STAG1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165977 | GEO | 2021/05/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The effect of STAG2 loss in Ewing sarcoma [ChIP-seq]

Project description:Ewing sarcoma is an aggressive malignancy characterized by oncogenic rearrangements of the EWS gene with an ETS-family transcription factor, most commonly FLI. Recent comprehensive next-generation sequencing efforts have revealed few other highly recurrent mutations in this disease apart from loss-of-function mutations in STAG2 which occur in 15-20% of tumors. STAG2 is a member of the cohesin complex, which regulates sister chromatid alignment during mitosis and epigenetic regulation of gene expression. While some studies suggest that loss of STAG2 is associated with the development of aneuploidy, this is not the case in Ewing sarcoma. To investigate whether STAG2 loss effects epigenetic regulation of gene expression in Ewing sarcoma, we developed isogenic Ewing sarcoma cell lines with STAG2 knockout. We found that Ewing sarcoma cells engineered for loss of STAG2 maintain an intact cohesion complex that alternately incorporates STAG1.

2021-05-14 | GSE165783 | GEO

The effect of STAG2 loss in Ewing sarcoma [ATAC-Seq]

2021-05-14 | GSE116494 | GEO

The effect of STAG2 loss in Ewing sarcoma [RNA-Seq]

2021-05-14 | GSE116492 | GEO

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1

Project description:Cohesin complexes carrying STAG1 or STAG2 organize the genome into chromatin loops. STAG2 loss-of-function mutations promote metastasis in Ewing sarcoma, a pediatric cancer that is driven by the fusion transcription factor EWS-FLI1. We have integrated transcriptomic data from patients and cellular models to identify a STAG2-dependent gene signature associated with worse prognosis. Subsequent genomic profiling and high-resolution chromatin interaction data from Capture Hi-C indicate that cohesin-STAG2 facilitates the communication between EWS-FLI1-bound long GGAA repeats acting as neoenhancers and their target promoters. Changes in CTCF-dependent chromatin contacts, unrelated to EWS-FLI1 binding, also contribute to the aggressive phenotype. STAG1 is unable to compensate for STAG2 loss and chromatin-bound cohesin is severely decreased, while levels of the processivity factor NIPBL remain unchanged, resulting in altered DNA looping dynamics. These results illuminate how STAG2 loss rewires the Ewing sarcoma chromatin interactome to promote metastasis and provide a list of potential biomarkers and therapeutic targets.

2024-09-18 | GSE267222 | GEO

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1

2024-09-18 | GSE267221 | GEO

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1

2024-09-18 | GSE267220 | GEO

ChIP-seq data in A673 & TC71 Ewing cell lines (STAG1 and STAG2 knock-out)

Project description:STAG2, a member of cohesin, is one of the most recurrently mutated genes in human cancer. Here, we investigated STAG2 function in the context of Ewing sarcoma, an aggressive bone tumor driven by EWS-FLI1 oncogene chimeric transcription factor. Using a CRISPR/Cas9 approach, we generated three STAG2 knock-out isogenic clones (A673_SA2m#1, TC71_SA2m#1 and TC71_SA2m#2) derived from A673 and TC71 STAG2 wild type (WT) Ewing sarcoma cell line. Similarly, a STAG1 knock-out isogenic clone (A673_SA1m#1) was generated. Finally, a STAG2 rescue model (A673_SA2r) was generated by correcting the CRISPR mutation in the A673_SA2m#1 model. These STAG1/2 proficient and deficient models were profiled by ChIP-seq for EWS-FLI1, CTCF, cohesin members, and histone marks and allowed to highlight a global conservation of binding for these marks upon STAG2 mutation.

2021-04-29 | GSE133154 | GEO

HiChIP data in A673 & TC71 Ewing cell lines (STAG1 and STAG2 knock-out)

Project description:STAG2, a member of cohesin, is one of the most recurrently mutated genes in human cancer. Here, we investigated STAG2 function in the context of Ewing sarcoma. Using a CRISPR/Cas9 approach, we generated two STAG2 knock-out isogenic clones (A673_SA2m#1 and TC71_SA2m#2) derived from A673 and TC71 STAG2 wild type (WT) Ewing sarcoma cell line. A STAG2 rescue model (A673_SA2r) was generated by correcting the CRISPR mutation in the A673_SA2m#1 model. These STAG1/2 proficient and deficient models were profiled by CTCF HiChIP experiments. STAG2 isogenic models were also profiled by H3K27ac HiChIP experiments. Analyses of HiChIP data allowed to show that STAG2 promotes CTCF-anchored loop extrusion and cis-promoter and -enhancer interactions.

2021-04-29 | GSE133227 | GEO

STAG2 Loss Rewires Oncogenic and Developmental Programs to Promote Metastasis in Ewing Sarcoma

Project description:Adane B, Alexe G, Seong BKA, Lu D, Hwang E, Hnisz D, Lareau CA, Ross L, Lin S, Dela Cruz FS, Richardson M, Weintraub AS, Wang S, Balboni-Iniguez A, Dharia NV, Conway AS, Robichaud AL, Tanenbaum B, Krill-Burger JM, Vazquez F, Schenone M, Berman JN, Kung A, Carr SA, Aryee MJ, Young RA, Crompton BD, Stegmaier K. 2021 Cancer Cell. The core cohesin subunit STAG2 is recurrently mutated in Ewing sarcoma but its biological role is less clear. Herein, we demonstrate that cohesin complexes containing STAG2 occupy enhancer and polycomb repressive complex (PRC2) marked regulatory regions. Genetic suppression of STAG2 leads to a compensatory increase in cohesin-STAG1 complexes, but not in enhancer rich regions, and results in reprogramming of cis-chromatin interactions. Strikingly, in STAG2 knockout cells, the oncogenic genetic program driven by the fusion transcription factor EWS/FLI1 was highly perturbed, in part due to altered enhancer-promoter contacts. Moreover, loss of STAG2 also disrupted PRC2-mediated regulation of gene expression. Combined, these transcriptional changes converged to modulate EWS/FLI1, migratory and neurodevelopmental programs. Finally, consistent with clinical observations, functional studies revealed that loss of STAG2 enhances the metastatic potential of Ewing sarcoma xenografts. Our findings demonstrate that STAG2 mutations can alter chromatin architecture and transcriptional programs to promote an aggressive cancer phenotype.

| MSV000082954 | MassIVE

RNA-seq data (STAG2 WT and mutated Ewing sarcoma cell lines)

Project description:STAG2 is a member of cohesin complex and its gene is one of the most recurrently mutated in human cancer including in Ewing sarcoma. Here, we investigated STAG2 function in the context of Ewing sarcoma and performed transcriptome profiling of a panel of 15 WT and 15 mutated STAG2 established Ewing sarcoma cell lines.

2021-04-29 | GSE171948 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data