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Super-enhancer-associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells

ABSTRACT: Super-enhancer-associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells

PROVIDER: PRJNA835104 | ENA |

REPOSITORIES: ENA

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Super-enhancer-associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells [ChIP-Seq]

Project description:Neuroblastoma is a pediatric tumor that accounts for more than 15% of cancer-related deaths in children. Survival chances for high-risk patients are less than 50%. Retinoic acid treatment is part of the maintenance therapy given to neuroblastoma patients; however, not all tumors respond to retinoic acid-mediated differentiation. Among neuroblastoma tumors, two phenotypically distinct cell types-adrenergic (ADRN) and mesenchymal (MES), have been identified based on their super-enhancer landscape and transcriptional core regulatory circuitries. We hypothesized that distinct super-enhancers in these different tumor cells could mediate differential response to retinoic acid. To this end, we treated four different neuroblastoma cell lines, comprising both ADRN (MYCN amplified and non-amplified) and MES subtypes, with retinoic acid and studied the super-enhancer landscape upon treatment and after removal of retinoic acid. Using H3K27ac ChIP-seq paired with RNA-seq, we compared the super-enhancers in cells that respond to retinoic acid-mediated differentiation versus those that fail to differentiate. We identified unique super-enhancers associated with cells differentiation; however, even among cells that respond to treatment, there was heterogeneity upon removal of retinoic acid, with MYCN amplified cells remaining differentiated whereas MYCN non-amplified cells reverted to a proliferative state. This study identifies regulatory super-enhancers as a plausible mechanism behind the differential response to retinoic acid-mediated differentiation.

2022-07-28 | GSE202239 | GEO

Super-enhancer-associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells [RNA-seq]

2022-07-28 | GSE201179 | GEO

Super-enhancer-associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells [ChIP-Seq]

Project description:Super-enhancer-associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells [ChIP-Seq]

| PRJNA835108 | ENA

Super-enhancer-associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells [RNA-seq]

Project description:Super-enhancer-associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells [RNA-seq]

| PRJNA828609 | ENA

Super-enhancer associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells.

Project description:Neuroblastoma is a pediatric tumour that accounts for more than 15% of cancer-related deaths in children. High-risk tumours are often difficult to treat, and patients' survival chances are less than 50%. Retinoic acid treatment is part of the maintenance therapy given to neuroblastoma patients; however, not all tumours differentiate in response to retinoic acid. Within neuroblastoma tumors, two phenotypically distinct cell types have been identified based on their super-enhancer landscape and transcriptional core regulatory circuitries: adrenergic (ADRN) and mesenchymal (MES). We hypothesized that the distinct super-enhancers in these different tumour cells mediate differential response to retinoic acid. To this end, three different neuroblastoma cell lines, ADRN (MYCN amplified and non-amplified) and MES cells, were treated with retinoic acid, and changes in the super-enhancer landscape upon treatment and after subsequent removal of retinoic acid was studied. Using ChIP-seq for the active histone mark H3K27ac, paired with RNA-seq, we compared the super-enhancer landscape in cells that undergo neuronal differentiation in response to retinoic acid versus those that fail to differentiate and identified unique super-enhancers associated with neuronal differentiation. Among the ADRN cells that respond to treatment, MYCN-amplified cells remain differentiated upon removal of retinoic acid, whereas MYCN non-amplified cells revert to an undifferentiated state, allowing for the identification of super-enhancers responsible for maintaining differentiation. This study identifies key super-enhancers that are crucial for retinoic acid-mediated differentiation.

| S-EPMC9485839 | biostudies-literature

Super-enhancer-associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-07-28 | GSE202241 | GEO

Cis-Regulatory Circuits Regulating NEK6 Kinase Overexpression in Transformed B Cells Are Super-Enhancer-Independent (4C-seq)

Project description:Alterations in distal regulatory elements that control gene expression underlie many diseases, including cancer. Epigenomic analyses of normal and diseased cells have produced correlative predictions for connections between dysregulated enhancers and target genes involved in pathogenesis. However, with few exceptions, these predicted cis-regulatory circuits remain untested. Here, we dissect cis-regulatory circuits that lead to overexpression of NEK6, a mitosis-associated kinase, in human B cell lymphoma. We find that only a minor subset of predicted enhancers is required for NEK6 expression. Indeed, an annotated super-enhancer is dispensable for NEK6 overexpression and for maintaining the architecture of a B cell-specific regulatory hub. A CTCF cluster serves as a chromatin and architectural boundary to block communication of the NEK6 regulatory hub with neighboring genes. Our findings emphasize that validation of predicted cis-regulatory circuits and super-enhancers is needed to prioritize transcriptional control elements as therapeutic targets.

2017-02-23 | GSE87322 | GEO

Cis-Regulatory Circuits Regulating NEK6 Kinase Overexpression in Transformed B Cells Are Super-Enhancer-Independent (RNA-seq)

2017-02-23 | GSE87320 | GEO

Tumor-suppressive disruption of cancer subtype-associated super enhancer1 circuits by small molecule treatment

Project description:Tumor-suppressive disruption of cancer subtype-associated super enhancer1 circuits by small molecule treatment

| PRJEB54584 | ENA

Cis-Regulatory Circuits Regulating NEK6 Kinase Overexpression in Transformed B Cells Are Super-Enhancer-Independent

Project description:Cis-Regulatory Circuits Regulating NEK6 Kinase Overexpression in Transformed B Cells Are Super-Enhancer-Independent

| PRJNA344333 | ENA