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Histone serotonylation regulates ependymoma tumorigenesis through neurodevelopmental pathways

ABSTRACT: Histone serotonylation regulates ependymoma tumorigenesis through neurodevelopmental pathways

PROVIDER: PRJNA1031155 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26490715.fastq.gz	Fastqsanger.gz
	SRR26490716.fastq.gz	Fastqsanger.gz
	SRR26490717.fastq.gz	Fastqsanger.gz
	SRR26490718.fastq.gz	Fastqsanger.gz
	SRR26490719.fastq.gz	Fastqsanger.gz

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Histone serotonylation regulates ependymoma tumorigenesis through neurodevelopmental pathways [ChIP-Seq]

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Histone serotonylation regulates ependymoma tumorigenesis through neurodevelopmental pathways [RNA-seq]

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Histone serotonylation regulates ependymoma tumorigenesis through neurodevelopmental pathways

Project description:Bidirectional communication between tumors and neurons has emerged as a key facet of the tumor microenvironment that drives malignancy. Another hallmark feature of cancer is epigenomic dysregulation, where alterations in gene expression influences cell states and interactions with the tumor microenvironment. Using the pediatric brain tumor ependymoma (EPN) as a model, we found that inhibition of histone serotonylation blocks EPN tumorigenesis and regulates expression of a core set of developmental transcription factors (TFs). High-throughput, in vivo screening of these TFs revealed that ETV5 promotes EPN tumorigenesis and functions by enhancing repressive chromatin states. Neuropeptide Y (NPY) is amongst the genes repressed by ETV5 and its overexpression suppresses EPN tumor progression and tumor-associated network hyperactivity via synaptic remodeling. Collectively, these studies identify histone serotonylation as a key driver of EPN tumorigenesis, while further revealing how neuronal signaling, neuro-epigenomics, and developmental programs are intertwined to drive malignancy in brain cancer.

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Histone serotonylation regulates ependymoma tumorigenesis through neurodevelopmental pathways [ChIP-Seq]

Project description:To profile H3K4me3Q5Ser (5HT-H3) distribution in mouse ZFTA-RELA ependymoma tumors Furthermore, we also sought to examine H3K27ac and H3K27me3 distribution in mouse ZFTA-RELA ependymoma versus ETV5 overexpressing tumors

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Histone serotonylation regulates ependymoma tumorigenesis through neurodevelopmental pathways [RNA-seq]

Project description:To profile gene expression differences between mouse non-tumor cortex versus ZFTA-RELA ependymoma versus ETV5 overexpressing tumors Furthermore, we also sought to profile gene expression differences between ZFTA-RELA ependymoma versus NPY overexpressing tumor

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Histone serotonylation regulates ependymoma tumorigenesis through neurodevelopmental pathways

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

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Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome [RNA-seq]

Project description:Brain development requires appropriate regulation of serotonin (5-HT) signaling from distinct tissue sources across embryogenesis. At the maternal-fetal interface, the placenta is thought to be an important contributor of offspring brain 5-HT and is critical to overall fetal health. Yet, how placental 5-HT is acquired, and the mechanisms through which 5-HT influences placental functions, are not well understood. Recently, our group identified a novel epigenetic role for 5-HT, in which 5-HT can be added to histone proteins to regulate transcription, a process called H3 serotonylation. Here, we show that H3 serotonylation undergoes dynamic regulation during placental development, corresponding to gene expression changes that are known to influence key metabolic processes. Using transgenic mice, we demonstrate that placental H3 serotonylation largely depends on 5-HT uptake by the serotonin transporter (Sert/Slc6a4). Sert deletion robustly reduces enrichment of H3 serotonylation across the placental genome, and disrupts neurodevelopmental gene networks in offspring brain tissues. Thus, these findings suggest a novel role for H3 serotonylation in coordinating placental transcription at the intersection of maternal physiology and offspring brain development.

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Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome

Project description:Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome

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Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome [ChIP-seq]

Project description:Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome [ChIP-seq]

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