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SET1B facilitates activation of the hypoxia response through site-specific histone methylation

ABSTRACT: SET1B facilitates activation of the hypoxia response through site-specific histone methylation

PROVIDER: PRJNA714950 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12781720_1.fastq.gz	Fastqsanger.gz
	SRR12781720_2.fastq.gz	Fastqsanger.gz
	SRR12781721_1.fastq.gz	Fastqsanger.gz
	SRR12781721_2.fastq.gz	Fastqsanger.gz
	SRR12781722_1.fastq.gz	Fastqsanger.gz

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SET1B facilitates activation of the hypoxia response through site-specific histone methylation

Project description:Hypoxia-inducible transcription factors (HIFs) are fundamental to the cellular adaptation to low oxygen levels but how they interact with chromatin and efficiently activate their target genes is unclear. Using genome-wide mutagenesis in human cancer cells, we define genes required for HIF transcriptional activation, and identify a requirement for the Histone 3 lysine 4 (H3K4) methyltransferase SET1B. Loss of SET1B leads to a selective reduction in HIF transcriptional activity in hypoxia, with SET1B driving expression of genes involved in angiogenesis rather than glycolysis, resulting in impaired tumour establishment in SET1B deficient xenografts. Mechanistically, we show that SET1B is itself oxygen regulated, accumulates on chromatin in hypoxia, and is recruited to HIF target genes through HIF-1a. Accordingly, we show that the hypoxic induction of H3K4me3 at specific HIF targets is both HIF and SET1B dependent, and when impaired, decreases promotor acetylation and gene expression. Together, these findings reveal SET1B as a determinant of site-specific histone methylation and provide insight into how HIF target genes are differentially regulated.

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SET1B facilitates activation of the hypoxia response through site-specific histone methylation [ChIP-seq_2]

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SET1B facilitates activation of the hypoxia response through site-specific histone methylation

Project description:SET1B facilitates activation of the hypoxia response through site-specific histone methylation

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Project description:SET1B facilitates activation of the hypoxia response through site-specific histone methylation [ChIP-seq_1]

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SET1B facilitates activation of the hypoxia response through site-specific histone methylation [ChIP-seq_2]

Project description:SET1B facilitates activation of the hypoxia response through site-specific histone methylation [ChIP-seq_2]

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SET1B facilitates activation of the hypoxia response through site-specific histone methylation

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