title: Extensive regulation of the non-coding transcriptome by hypoxia: role of HIF in releasing paused RNApol2.
abstract: 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.
authors.affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Hani
authors.initials: H
authors.lastname: Choudhry
authors.forename: Johannes
authors.initials: J
authors.lastname: Schödel
authors.forename: Spyros
authors.initials: S
authors.lastname: Oikonomopoulos
authors.forename: Carme
authors.initials: C
authors.lastname: Camps
authors.forename: Steffen
authors.initials: S
authors.lastname: Grampp
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ratcliffe
authors.forename: Jiannis
authors.initials: J
authors.lastname: Ragoussis
authors.forename: David R
authors.initials: DR
authors.lastname: Mole
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D015687:Cell Hypoxia; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012319:RNA Polymerase II; D012333:RNA, Messenger; D022661:RNA, Untranslated; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human