Extensive regulation of the non-coding transcriptome by hypoxia: role of HIF in releasing paused RNApol2

Hypoxia is central to both ischaemic and neoplastic diseases. However, the non-coding transcriptional response to hypoxia is largely uncharacterized. We undertook integrated genomic analyses of both non-coding and coding transcripts using massively parallel sequencing and interfaced this data with p...

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Bibliographic Details
Main Authors: Choudhry, H, Schödel, J, Oikonomopoulos, S, Camps, C, Grampp, S, Harris, AL, Ratcliffe, PJ, Ragoussis, J, Mole, DR
Format: Journal article
Language:English
Published: EMBO Press 2013
Description
Summary:Hypoxia is central to both ischaemic and neoplastic diseases. However, the non-coding transcriptional response to hypoxia is largely uncharacterized. We undertook integrated genomic analyses of both non-coding and coding transcripts using massively parallel sequencing and interfaced this data with pan-genomic analyses of hypoxia-inducible factor (HIF) and RNApol2 binding in hypoxic cells. These analyses revealed that all classes of RNA are profoundly regulated by hypoxia and implicated HIF as a major direct regulator of both the non-coding and coding transcriptome, acting predominantly through release of pre-bound promoter-paused RNApol2. These findings indicate that the transcriptional response to hypoxia is substantially more extensive than previously considered.