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Chromatin run-on and sequencing maps the transcriptional regulatory landscape of glioblastoma multiforme

ABSTRACT: Chromatin run-on and sequencing maps the transcriptional regulatory landscape of glioblastoma multiforme

PROVIDER: PRJNA483346 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7616132.fastq.gz	Fastqsanger.gz
	SRR7616133.fastq.gz	Fastqsanger.gz
	SRR7616134.fastq.gz	Fastqsanger.gz
	SRR7616135.fastq.gz	Fastqsanger.gz

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Chromatin run-on and sequencing maps the transcriptional regulatory landscape of glioblastoma multiforme

Project description:The human genome encodes a variety of poorly understood RNA species that remain challenging to identify using existing genomic tools. We developed chromatin run-on and sequencing (ChRO-seq) to map the location of RNA polymerase using virtually any input sample, including samples with degraded RNA that are intractable to RNA-seq. We used ChRO-seq to map nascent transcription in primary human glioblastoma (GBM) brain tumors. Whereas enhancers discovered in primary GBMs resemble open chromatin in the normal human brain, rare enhancers activated in malignant tissue drive regulatory programs similar to the developing nervous system. We identified enhancers that regulate genes characteristic of each known GBM subtype, identified transcription factors that drive them, and discovered a core group of transcription factors that control the expression of genes associated with clinical outcomes. This study reveals the transcriptional basis of GBM and introduces ChRO-seq to map regulatory programs contributing to complex diseases.

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Chromatin run-on and sequencing maps the transcriptional regulatory landscape of glioblastoma multiforme.

Project description:The human genome encodes a variety of poorly understood RNA species that remain challenging to identify using existing genomic tools. We developed chromatin run-on and sequencing (ChRO-seq) to map the location of RNA polymerase for almost any input sample, including samples with degraded RNA that are intractable to RNA sequencing. We used ChRO-seq to map nascent transcription in primary human glioblastoma (GBM) brain tumors. Enhancers identified in primary GBMs resemble open chromatin in the normal human brain. Rare enhancers that are activated in malignant tissue drive regulatory programs similar to the developing nervous system. We identified enhancers that regulate groups of genes that are characteristic of each known GBM subtype and transcription factors that drive them. Finally we discovered a core group of transcription factors that control the expression of genes associated with clinical outcomes. This study characterizes the transcriptional landscape of GBM and introduces ChRO-seq as a method to map regulatory programs that contribute to complex diseases.

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