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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.

Original publication

DOI

10.1002/embr.201337642

Type

Journal article

Journal

EMBO Rep

Publication Date

01/2014

Volume

15

Pages

70 - 76

Keywords

Basic Helix-Loop-Helix Transcription Factors, Cell Hypoxia, Gene Expression Regulation, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, MCF-7 Cells, Promoter Regions, Genetic, Protein Binding, RNA Polymerase II, RNA, Messenger, RNA, Untranslated, Transcription, Genetic, Transcriptome