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TCF4 is a key mediator of cell identity in neuroblastoma and vulnerable to protein degradation by multiple epigenetic factors

ABSTRACT: TCF4 is a key mediator of cell identity in neuroblastoma and vulnerable to protein degradation by multiple epigenetic factors

PROVIDER: PRJNA918609 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22985555_1.fastq.gz	Fastqsanger.gz
	SRR22985555_2.fastq.gz	Fastqsanger.gz
	SRR22985556_1.fastq.gz	Fastqsanger.gz
	SRR22985556_2.fastq.gz	Fastqsanger.gz
	SRR22985557_1.fastq.gz	Fastqsanger.gz

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TCF4 is a key mediator of cell identity in neuroblastoma and vulnerable to protein degradation by multiple epigenetic factors [ChIP-seq]

Project description:Neuroblastomas (NBs) are aggressive pediatric tumors that are responsible for up to 15% of all pediatric cancer deaths. Two differentiation states exist in NB tumors, a majority of more committed ADRN tumor cells and a minority of neural crest cell (MES/NCC)-like cells. The transition between identity states is governed by different sets of master TFs that collectively form core regulatory circuitries (CRC) that drive high expression of downstream lineage-specific genes. In this study we aim to discover new lineage dependency factors in NB. Here, we identified the E-box transcription factor TCF4 (E2-2) not previously reported in NB to be a critical factor shared across both NB states and play important role in driving NB oncogenesis. We performed multiple functional and high-throughput analysis to delineate the unrecognized function of TCF4 in NB

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TCF4 is a key mediator of cell identity in neuroblastoma and vulnerable to protein degradation by multiple epigenetic factors [RNA-seq]

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TCF4 is a key mediator of cell identity in neuroblastoma and vulnerable to protein degradation by multiple epigenetic factors [RNA-seq]

Project description:TCF4 is a key mediator of cell identity in neuroblastoma and vulnerable to protein degradation by multiple epigenetic factors [RNA-seq]

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TCF4 is a key mediator of cell identity in neuroblastoma and vulnerable to protein degradation by multiple epigenetic factors [ChIP-seq]

Project description:TCF4 is a key mediator of cell identity in neuroblastoma and vulnerable to protein degradation by multiple epigenetic factors [ChIP-seq]

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TCF4 is a key mediator of cell identity in neuroblastoma and vulnerable to protein degradation by multiple epigenetic factors

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

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Mediator complex interaction partners organize the transcriptional network that defines neural stem cells

Project description:Mediator complex regulates transcription by connecting enhancers to promoters. High Mediator binding density defines super enhancers, which regulate cell-identity genes and oncogenes. Protein interactions of Mediator may explain its role in these processes but have not been identified comprehensively. Here we purify Mediator from neural stem cells (NSCs) and identify 75 protein-protein interaction partners. We identify super enhancers in NSCs and show that Mediator-interacting chromatin modifiers colocalise with Mediator at enhancers and super enhancers. Transcription factor families with high affinity for Mediator dominate enhancers and super enhancers and can explain genome-wide Mediator localization. We identify E-box transcription factor Tcf4 as a key regulator of NSCs. Tcf4 interacts with Mediator, colocalises with Mediator at super enhancers and regulates neurogenic transcription factor genes with super enhancers and broad H3K4me3 domains. Our data suggest that high binding-affinity for Mediator is an important organizing feature in the transcriptional network that determines NSC identity.

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Mediator complex interaction partners organize the transcriptional network that defines neural stem cells

Project description:The Mediator complex regulates transcription by connecting enhancers to promoters. High Mediator binding density is one defining feature of so-called super enhancers, which regulate cell-identity genes and oncogenes. Protein interactions of Mediator may explain its role in these processes but have not been identified comprehensively. Here we purify Mediator from neural stem cells (NSCs) and identify 77 novel protein-protein interaction partners. We identified super enhancers in NSCs and show that Mediator-interacting chromatin modifiers colocalise with Mediator at enhancers and super enhancers. Three transcription factor families with high affinity for Mediator dominate enhancers and super enhancers in NSCs and can explain genome-wide Mediator localization. We identify E-box transcription factor Tcf4 as a key regulator in NSCs. Tcf4 interacts with Mediator, colocalises and correlates with Mediator at super enhancers and regulates other neural transcription factors via super enhancers. Our data suggest that high binding-affinity for Mediator is an important organizing feature in the transcriptional network that determines NSC identity.

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2013-02-13 | E-GEOD-44287 | biostudies-arrayexpress

Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes [ChIP-Seq]

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