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.

Cited by papers we hold 12

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• MALAT1 Long Non-Coding RNA: Functional Implications · 2020
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• Hypoxia-induced lncRNA-AC020978 promotes proliferation and glycolytic metabolism of non-small cell lung cancer by regulating PKM2/HIF-1α axis · 2020
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• Hypoxia-induced switch in SNAT2/SLC38A2 regulation generates endocrine resistance in breast cancer · 2019
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• Inherent DNA‐binding specificities of the HIF‐1α and HIF‐2α transcription factors in chromatin · 2018
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• New horizons in hypoxia signaling pathways · 2017
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• Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1α co-activator driving oral cancer progression · 2017
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• Implication of Long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing · 2016
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• Metabolic and hypoxic adaptation to anti‐angiogenic therapy: a target for induced essentiality · 2015
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• TET1-Mediated Hydroxymethylation Facilitates Hypoxic Gene Induction in Neuroblastoma · 2014
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• Tumor hypoxia induces nuclear paraspeckle formation through HIF-2α dependent transcriptional activation of NEAT1 leading to cancer cell survival · 2014
  Corrected
• Integrated analysis of microRNA and mRNA expression and association with HIF binding reveals the complexity of microRNA expression regulation under hypoxia · 2014
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