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ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer [ChIP-Seq]

ABSTRACT: ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer [ChIP-Seq]

PROVIDER: PRJNA759603 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15688483.fastq.gz	Fastqsanger.gz
	SRR15688484.fastq.gz	Fastqsanger.gz
	SRR15688485_1.fastq.gz	Fastqsanger.gz
	SRR15688485_2.fastq.gz	Fastqsanger.gz
	SRR15688486_1.fastq.gz	Fastqsanger.gz

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ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer

Project description:ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer

| PRJNA759600 | ENA

ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer [ATAC-Seq]

Project description:ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer [ATAC-Seq]

| PRJNA759599 | ENA

ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer [RNA-Seq]

Project description:ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer [RNA-Seq]

| PRJNA759604 | ENA

ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer [RNA-Seq]

Project description:Treatment with androgen receptor pathway inhibitors (ARPIs) in prostate cancer leads to the emergence of resistant tumors characterized by lineage plasticity and divergent differentiation toward neuroendocrine lineage. We found that ARPIs induce a rapid epigenetic alteration mediated by large-scale chromatin remodeling to support activation of stem/neuronal transcriptional programs. We identified motifs for the proneuronal transcription factor ASCL1 to be enriched in hyper-accessible regions. ASCL1 acts as a driver of the lineage plastic, neuronal transcriptional program to support treatment resistance and neuroendocrine phenotype. Targeting ASCL1 switches the neuroendocrine lineage back to the luminal epithelial state. This effect is modulated by disruption of the polycomb repressive complex-2 and change the chromatin architecture in favor of luminal phenotype. Our study provides insights into the epigenetic alterations induced by ARPI governed by ASCL1, provides a proof of principle of targeting ASCL1 to reverse the neuroendocrine phenotype, support luminal conversion and re-addiction to ARPIs.

2022-03-30 | GSE183199 | GEO

ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer [ChIP-Seq]

2022-03-30 | GSE183198 | GEO

ASCL1 activates neuronal stem cell-like lineage programing through remodeling of the chromatin landscape in prostate cancer [ATAC-Seq]

2022-03-30 | GSE183196 | GEO

EWS-WT1 Oncogene Activates a Neuronal Reprogramming Factor ASCL1 and Mediates Partial Neural Differentiation

Project description:A chromosomal translocation fusion gene product EWS-WT1 is the defining genetic event in Desmoplastic Small Round Cell Tumor (DSRCT), a rare but aggressive tumor with a high rate of mortality. EWS-WT1 oncogene acts as an aberrant transcription factor that drives tumorigenesis, but the mechanism by which EWS-WT1 causes tumorigenesis is not well understood. To delineate the oncogenic mechanisms, we generated the EWS-WT1 fusion in the mouse using a gene targeting (knock-in) approach, enabling physiologic expression of EWS-WT1 under the native Ews promoter. We derived mouse embryonic fibroblasts (MEFs) and performed genome-wide expression profiling to identify transcripts directly regulated by EWS-WT1. Remarkably, expression of EWS-WT1 led to a dramatic induction of many neuronal genes. Notably, a neural reprogramming factor, ASCL1 (achaete-scute complex-like 1), was highly induced by EWS-WT1 in MEFs and in primary DSRCT. Further analysis demonstrated that EWS-WT1 directly binds to the proximal promoter region of ASCL1 and activates its transcription through multiple WT1-responsive elements. Depletion of EWS-WT1 in a DSRCT cell line resulted in severe reduction in ASCL1 expression and cell viability. Remarkably, when stimulated with neuronal induction media, cells expressing EWS-WT1 expressed neural markers and generated neurite-like projections. These results demonstrate for the first time that EWS-WT1 activates neural gene expression and is capable of directing partial neuronal differentiation, likely via ASCL1. These findings suggest that stimulating DSRCT tumor cells with biological or chemical agents that promote neural differentiation might be a useful approach to develop novel therapeutics against this incurable disease. mouse embryonic fibroblasts (MEFs) and performed genome-wide expression profiling to identify transcripts directly regulated by EWS-WT1 in 0 vs. 24 Hours in three replications (WT+KTS, or WT-KTS in 0, 24 H; CRE in 0 and 24H)

2014-09-11 | E-GEOD-53301 | biostudies-arrayexpress

EWS-WT1 Oncogene Activates a Neuronal Reprogramming Factor ASCL1 and Mediates Partial Neural Differentiation

2014-09-11 | GSE53301 | GEO

ASCL1 defines differentiation-competent GBM cells and directs neoplastic cells towards neuronal fate

Project description:We identified a subgroup of patient-derived glioblastoma (GBM) cells that express high levels of the neurogenic transcription factor, ASCL1, which predicts response to pharmacological inhibition of the Notch signaling pathway. Treatment of ASCL1hi GBM cells with a Notch signaling inhibitor induced a change in cell fate from neoplastic to neuronal. Importantly, acquisition of the neuronal fate was accompanied by a reduction in tumorigenic potential. Loss of ASCL1 in GBM cells rendered cells no longer responsive to Notch signaling inhibition and we determined ASCL1 is required for the competency of GBM cells to undergo neuronal differentiation. Enforced ASCL1 expression directed GBM cells towards a neuronal cell fate reminiscent of terminal differentiation. RNA-seq analysis of GBM cells treated with the Notch signaling inhibitor reveals neuronal target gene activation is associated with increased stoichiometric levels of ASCL1, suggesting threshold levels of ASCL1 in GBM cells governs neuronal differentiation. We demonstrate that neoplastic cells which retain expression of key neurogenic programs can have their fates redirected towards terminal differentiation. Directed fate specification to neuronal cell types by exploiting latent neurogenic programs may be a strategy to treat a subset of GBM patients. Our findings therefore highlight the potential of differentiation therapy for a subset of molecularly defined GBMs.

2017-07-21 | GSE96088 | GEO

FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis

Project description:FOXO transcription factors are central regulators of longevity from worms to humans. FOXO3 – the FOXO isoform associated with exceptional human longevity – preserves adult neural stem cell pools. Here we identify FOXO3 direct targets genome-wide in primary cultures of adult neural progenitor cells (NPCs). Interestingly, FOXO3-bound sites are enriched for motifs for bHLH transcription factors and FOXO3 shares common targets with the pro-neuronal bHLH transcription factor ASCL1/MASH1 in NPCs. Analysis of the chromatin landscape reveals that FOXO3 and ASCL1 are particularly enriched at the enhancers of genes involved in neurogenic pathways. Intriguingly, FOXO3 inhibits ASCL1-dependent neurogenesis in NPCs and direct neuronal conversion in fibroblasts. FOXO3 also restrains neurogenesis in vivo. Our study identifies a genome-wide interaction between the pro-longevity transcription factor FOXO3 and the cell fate determinant ASCL1, and raises the possibility that FOXO3’s ability to restrain ASCL1-dependent neurogenesis may help preserve the neural stem cell pool. ChIP-seq profiles of two transcription factors (FOXO3 and ASCL1) and three histone marks (H3K4me1, H3K4me3 and H3K27me3) in adult mouse neural progenitor cells.

2013-08-13 | E-GEOD-48336 | biostudies-arrayexpress

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