Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identifying the genomic regions co-bound by ASCL1 and mSWI/SNF remodelers during neural differentiation [ChIP-seq]

ABSTRACT: We interfeered with the ASCL1-mSWI/SNF interaction: to abolish ASCL1 function, we knocked out ASCL1 in human iPSCs, while we used the BRM014 inhibitor to block the mSWI/SNF ATPase activity. We then performed ASCL1 ChIPseq in DIV24 WT and BRM014-treated neural cultures, and SMARCB1 ChIPseq in DIV24 WT and ASCL1 KO neural cultures, when ASCL1 expression is highest.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214381 | GEO | 2023/03/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identifying the genomic regions where ASCL1 and mSWI/SNF remodelers are both required to regulate chromatin accessibility during neural differentiation [ATAC-seq]

Project description:We interfeered with the ASCL1-mSWI/SNF interaction: to abolish ASCL1 function, we knocked out ASCL1 in human iPSCs, while we used the BRM014 inhibitor to block the mSWI/SNF ATPase activity. We performed ATACseq in WT, ASCL1 KO, and BRM014-treated cells at DIV24, when ASCL1 expression is highest during neural differentiation.

2023-03-14 | GSE214380 | GEO

Identifying the transcriptional output associated with distal regulatory elements where ASCL1 interacts with mSWI/SNF remodelers to regulate neural differentiation [RNA-seq]

Project description:We interfeered with the ASCL1-mSWI/SNF interaction: to abolish ASCL1 function, we knocked out ASCL1 in human iPSCs, while we used the BRM014 inhibitor to block the mSWI/SNF ATPase activity. We then collected RNA from WT, ASCL1 KO and BRM014-treated cells at DIV24, when ASCL1 expression is highest during neural differentiation.

2023-03-14 | GSE214382 | GEO

Identifying the genomic regions co-bound by ASCL1 and mSWI/SNF remodelers during neural differentiation [ChIP-seq]

Project description:Identifying the genomic regions co-bound by ASCL1 and mSWI/SNF remodelers during neural differentiation [ChIP-seq]

| PRJNA885097 | ENA

Single cell transcriptomes of neurally differentiated wildtype and ASCL1-KO human iPSCs, in the presence of NOTCH inhibitor DAPT [scRNA-seq]

Project description:The roles of neurogenic pioneer transcription factors and chromatin remodelers have been characterized in that process in developing animal models and cancers. However how these factors interact with each other to regulate cell state transitions in human neurogenesis remains unclear. Here we investigated the activity of the pioneer proneural factor ASCL1 in an in vitro model of human neurogenesis. We found that ASCL1 expression characterizes a transitional state from cycling neural progenitor to post-mitotic neuron, and ASCL1 knockout impedes progenitor neuronal differentiation. ASCL1 binds to genomic targets to regulate loci promoting differentiation by different mechanisms. Acting as a classical pioneer transcription factor, its binding to compacted chromatin is required to induce transcriptional activity. At other loci, it acts as a non-pioneer chromatin remodeler, accessing permissive chromatin to further increase chromatin accessibility. We show that ASCL1 interacts with ATPase-active BAF mSWI/SNF chromatin remodelers at cis-regulatory elements, altering the chromatin regulatory landscape at a subset of target genes. This cooperative function is predominant at sites of non-pioneer chromatin remodeler function where ASCL1 requires mSWI/SNF for DNA binding while ASCL1 classical pioneer activity does not involve significant mSWI/SNF binding. Our work establishes novel roles for ASCL1 and for an interaction with mSWI/SNF in regulating epigenetic states in human neurogenesis.

2023-03-14 | GSE214700 | GEO

Identifying the genomic regions where ASCL1 and mSWI/SNF remodelers are both required to regulate chromatin accessibility during neural differentiation [ATAC-seq]

Project description:Identifying the genomic regions where ASCL1 and mSWI/SNF remodelers are both required to regulate chromatin accessibility during neural differentiation [ATAC-seq]

| PRJNA885098 | ENA

Identifying the transcriptional output associated with distal regulatory elements where ASCL1 interacts with mSWI/SNF remodelers to regulate neural differentiation [RNA-seq]

Project description:Identifying the transcriptional output associated with distal regulatory elements where ASCL1 interacts with mSWI/SNF remodelers to regulate neural differentiation [RNA-seq]

| PRJNA885099 | ENA

Non-Canonical BAF and mSWI/SNF Regulates POU2F3 and are Selective Targetable Dependencies for POU2F3-Positive Small Cell Lung Cancer

Project description:~12% of SCLCs are marked by the lineage transcription factor POU2F3, which is essential in all POU2F3-positive SCLCs. Thus, approaches to directly or indirectly inhibit POU2F3 could lead to new therapeutic strategies for POU2F3-positive SCLCs. Here we use a positive selection screening strategy where endogenous POU2F3 is fused to the suicide gene DCK*. Cells that express endogenous POU2F3-DCK* are killed in the presence of the nucleoside analog BVdU and only cells that downregulate the POU2F3-DCK* fusion survive. Genome-wide CRISPR/Cas9 resistance screens with BVdU in POU2F3-DCK* cells uncovered that inactivation of SMARCD1 or BRD9, both components of the non-canonical BAF (ncBAF) complex, markedly downregulate endogenous POU2F3. We find that all POU2F3-positive SCLC cell lines relative to ASCL1-positive and NEUROD1-positive cell lines, are exquisitely sensitive to mSWI/SNF complex inhibition using SMARCA2/4 inhibitors; while pure non-neuroendocrine POU2F3-positive SCLC cell lines are highly sensitive to ncBAF complex inhibition using highly selective BRD9 degraders. Mechanistically, BRD9 binds and regulates POU2F3 target genes including POU2F3 itself. BRD9 degraders or SMARCA2/4 inhibitors robustly decrease accessibility of POU2F3 target genes effectively shutting off POU2F3 function. Moreover, BRD9 degraders or SMARCA2/4 inhibitors decrease tumor growth and increase survival of mice bearing non-neuroendocrine POU2F3 xenografts. This works shows that mSWI/SNF and ncBAF tightly regulate POU2F3 expression and activity and nominate mSWI/SNF or ncBAF inhibition as druggable therapeutic strategies to selectively target POU2F3-positive SCLCs.

2024-06-14 | GSE249362 | GEO

Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer

Project description:Small cell lung cancers (SCLC) are comprised of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLC, ~12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities for this subtype. Here using genome-scale CRISPR/Cas9-based screens reporting on POU2F3 expression in SCLC cell lines, we define mSWI/SNF complexes, including non-canonical BAF complexes (ncBAF), as top regulators of POU2F3 and dependencies specific to the POU2F3-positive subtype. Notably, clinical-grade pharmacologic mSWI/SNF complex inhibition attenuates proliferation of all POU2F3-positive SCLCs, while disruption of ncBAF via BRD9 degradation is uniquely effective in pure non-neuroendocrine POU2F3-SCLCs. mSWI/SNF complexes maintain accessibility over gene loci central to POU2F3-mediated gene regulatory networks. Finally, chemical targeting of SMARCA4/2 mSWI/SNF ATPases and BRD9 decrease POU2F3-SCLC tumor growth and increase survival in vivo. Taken together, these results define mSWI/SNF-mediated global governance of the POU2F3 oncogenic program and suggest mSWI/SNF inhibition as a therapeutic strategy in SCLC.

2024-06-14 | GSE249258 | GEO

Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation

Project description:Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation

| PRJNA885095 | ENA

mSWI/SNF functional genomic characterization of SMARCB1 mutants in SMARCB1-null and heterozygous settings

Project description:Chromatin remodeling complexes regulate gene expression by shifting, evicting, and exchanging nucleosomes along the chromosomes of eukaryotic organisms. The mammalian SWI/SNF chromatin remodeling complex (mSWI/SNF or BAF) is mutated in over 20% of human cancers and loss of the SMARCB1 gene, encoding the BAF47 protein subunit, results in one of the most aggressive and lethal pediatric cancers. An accumulation of point mutations occurs at the C-terminal end of the protein, for which the functional ramifications are unknown. We previously demonstrated that reintroduction of SMARCB1 in SMARCB1-null malignant rhabdoid tumor cells results in a genome-wide increase of mSWI/SNF complex occupancy coupled with activation of PRC2-repressed genes. Here, we study the functional consequences that these point mutations exert on mSWI/SNF complex activity in SMARCB1-deficient tumor cells and extend this investigation to a CRISPR/Cas9-mediated SMARCB1-heterozygous mutant induced pluripotent stem cell. Intriguingly, we observe that the mutant complexes bind similarly to wild-type SMARCB1 complexes at enhancers throughout the genome but often fail to transcriptionally activate nearby genes in a cis-regulatory manner.

2019-11-21 | GSE124903 | 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