Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Loss of ARID1A leads to a cold tumor phenotype via suppression of IFNγ signaling

ABSTRACT: The collapse of inflammatory signaling that recruits cytotoxic immune cells to the tumor microenvironment contributes to the immunologically cold tumor phenotype in neuroblastoma (NB) and is a barrier to NB immunotherapy. Multiple studies have reported that MYCN amplification, a trait of high-risk NB, correlates with a loss of inflammatory signaling; but MYCN also correlates with 1p36 deletions in NB where the SWI/SNF chromatin remodeling complex subunit ARID1A (1p36.11) is located. ARID1A is known to support inflammatory signaling in adult cancers but its role in NB inflammatory signaling is unexplored. We find MYCN overexpression causes a stronger and ARID1A knockdown causes a weaker inflammatory response to interferon-gamma (IFNγ). ARID1A silencing reduces IFNγ induced gene signatures for the transcription factor interferon response factor 1 (IRF1). We found ARID1A is a functional interactor of IRF1 by co-immunoprecipitation studies, and ARID1A silencing causes loss of activating chromatin marks at the IRF1 target gene CXCL10. We model that IRF1 uses ARID1A containing SWI/SNF to promote IRF1’s target genes in response to IFNγ. This work finds that ARID1A is a critical regulator of inflammatory signaling in NB and provides rationale for testing immune therapies in MYCN amplified NB that are effective in adult ARID1A mutated cancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE277050 | GEO | 2025/01/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Targeting SWI/SNF ATPases reduces cell invasiveness and plasticity in core transcription factors-addicted neuroblastoma

Project description:Neuroblastoma (NB) comprises mesenchymal (MES) and adrenergic (ADRN) subtypes, and the cell identity is determined by core transcription factors (TFs). However, the binding mechanism of these TFs to DNA and the epigenetic mechanisms governing NB plasticity remain unclear. In this study, we investigated the impact of targeting SWI/SNF ATPases with SMARCA2/4 dual degraders on NB cells. Our results revealed that depletion of SWI/SNF ATPases compacted cis-regulatory elements, diminished enhancer activity, and displaced core TFs (MYCN, HAND2, PHOX2B, and GATA3) from DNA, suppressing transcriptional programs linked to plasticity and invasiveness. These findings underscore the pivotal role of SWI/SNF ATPases in driving NB progression, positioning them as promising therapeutic targets.

2024-08-28 | GSE240724 | GEO

Targeting SWI/SNF ATPases reduces cell invasiveness and plasticity in core transcription factors-addicted neuroblastoma [ATAC-seq]

2024-08-28 | GSE240588 | GEO

Targeting SWI/SNF ATPases reduces cell invasiveness and plasticity in core transcription factors-addicted neuroblastoma [RNA-seq]

2024-08-28 | GSE240590 | GEO

Targeting SWI/SNF ATPases reduces cell invasiveness and plasticity in core transcription factors-addicted neuroblastoma [ChIP-seq]

2024-08-28 | GSE240589 | GEO

ChIP-seq analysis of Arid1a and C/ebpÎ± in the mouse livers

Project description:Arid1a is the subunit of SWI/SNF complex, which was reported to guide SWI/SNF to DNA. Here, we found that loss of Arid1a in the liver and other adult tissues results in improved organ regeneration. Within SWI/SNF complexes, Arid1a physically interacts with C/ebpÎ±, a hepatocyte transcription factor that drives maturation and limits proliferation. Genome-wide analysis showed that loss of Arid1a reduces the recruitment and activity of C/ebpÎ± on target promoters, resulting in expression programs that favor regeneration and cellular fitness during injury. Arid1a binding is enriched in promoters near transcriptional start sites (TSSs), and C/ebpÎ± binds at precisely the same positions, indicating that Arid1a facilitates C/ebpÎ± binding across the genome. Perfuse and isolate primary hepatocytes from mice livers, analysis of genomic occupancy of C/ebpÎ± and H3K4me2 in hepatocytes from Arid1a WT and Arid1a liver specific KO mice by ChIP-seq. Analysis of genomic occupancy of Arid1a in the hepatocytes from V5-Arid1a transgenic mouse by ChIP-seq.

2016-03-30 | E-GEOD-65167 | biostudies-arrayexpress

ARID-DNA interactions are essential for SWI/SNF function

Project description:Every known SWI/SNF chromatin-remodeling complex incorporates an ARID DNA binding domain-containing subunit. Despite being a ubiquitous component of these complexes, physiological roles for this domain remain undefined. We screened an N-ethyl-N-nitrosurea (ENU) mutagenized library for ARID domain point mutations and generated an Arid1a/Baf250a hypomorphic allele. The mutant ARID1a (V1068G) protein is stably expressed at wild-type levels, and it is capable of assembling into a SWI/SNF complex with in vitro mononucleosome disruption activity. However, its capacity to bind DNA is lost. Consistent with defective DNA binding, mutant protein occupancy at known SWI/SNF target genes is decreased. Loss of DNA binding is associated with concurrent changes in SWI/SNF target gene expression. Mutant embryos manifest heart defects, fail to establish proper yolk sac vasculature, and exhibit hemorrhaging. As a result of these phenotypes, mutant embryos fail to establish proper circulation, culminating in ischemic arrest in utero between days 9.5 and 11.5. These data support a role for ARID1a-containing, BAF-A complexes in heart and extraembryonic vascular development, and indicate the ARID domain of ARID1a is essential in this regard. Hence, intrinsic ARID subunit-DNA interactions are required for normal SWI/SNF function in vivo. Four-condition experiment, wild-type vs Baf250a/Arid1a^V1068G/V1068G yolk sacs isolated at E8.5 and E9.5. Biological replicates: 3 per condition.

2012-01-15 | E-GEOD-32116 | biostudies-arrayexpress

RNA-seq transcriptonal profiling in partial hepatectomy liver tissues in Arid1a WT and liver specific KO mice.

Project description:Arid1a is the subunit of SWI/SNF complex, which was reported to guide SWI/SNF to DNA. Here, we found that loss of Arid1a in the liver results in improved liver regeneration after partial hepatectomy.Genome-wide analysis showed that after hepatectomy,loss of Arid1a reduces the recruitment and activity of E2F4 on target promoters, resulting in expression programs that favor regeneration during injury.RNAseq shows transcriptional profiling in WT and Arid1a LKO livers pre- and post-hepatectomy, which confirmed the E2F4 target genes and cell cycle genes were upregulated after hepatectomy. After partial hepatectomy, liver transcriptional profiling in WT and Arid1a liver specific KO mice were generated by RNA-seq analysis.

2016-03-30 | E-GEOD-76926 | biostudies-arrayexpress

ARID1A Loss in Neuroblastoma Promotes the Adrenergic-to-Mesenchymal Transition by Regulating Enhancer-Mediated Gene Expression [ChIP-seq]

Project description:Gene mutations in components of SWI/SNF chromatin-remodeling complexes are found in approximately 20% of all human cancers, with ARID1A being the most frequently mutated subunit. In neuroblastoma, sequence alterations of ARID1A were identified in 6% of primary tumors and cell lines, and this gene is hemizygously deleted in at least 87% of cases with chromosome 1p deletion, which almost always accompanies MYCN gene amplification and is the most common deletions in high-risk subtypes of this tumor. However, the role of ARID1A haploinsufficiency in neuroblastoma pathogenesis and the mechanisms involved remain unclear. Here, we show that disruption of ARID1A homologs in a zebrafish model accelerates the onset and increases the penetrance of MYCN-driven neuroblastoma by increasing cell proliferation in the sympathoadrenal lineage. Depletion of ARID1A in human NGP neuroblastoma cells promoted the adrenergic-to-mesenchymal transition with changes in enhancer-mediated gene expression due to alterations in the genomic occupancies of two distinct SWI/SNF assemblies, BAF and PBAF. Our findings indicate that ARID1A is a haploinsufficient tumor suppressor in MYCN-driven neuroblastoma, whose depletion enhances tumor development and promotes the emergence of the more drug resistant mesenchymal cell state.

2020-07-20 | GSE134626 | GEO

ARID1A Loss in Neuroblastoma Promotes the Adrenergic-to-Mesenchymal Transition by Regulating Enhancer-Mediated Gene Expression [RNA-seq]

2020-07-20 | GSE134631 | GEO

ChIP-seq analysis of E2f4, H3K4me2 and H3K27ac in the mouse livers

Project description:Arid1a is the subunit of SWI/SNF complex, which was reported to guide SWI/SNF to DNA. Here, we found that loss of Arid1a in the liver results in improved liver regeneration after partial hepatectomy.Genome-wide analysis showed that after hepatectomy,loss of Arid1a reduces the recruitment and activity of E2F4 on target promoters, resulting in expression programs that favor regeneration during injury. Correspondingly, these promoters showed increased H3k4me2 and H3k27ac marks, indicating de-repression of these E2f target genes. The post partial hepatectomy mice liver cells were fixed and isolated, analysis of genomic occupancy of E2f4,H3K4me2,H3K27ac in hepatocytes from Arid1a WT and Arid1a liver specific KO mice by ChIP-seq.

2016-03-30 | E-GEOD-76927 | biostudies-arrayexpress

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