The hypoxia-inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens

Research output: Contribution to journalArticlepeer-review


  • Christoph Loenarz
  • Anna Boleininger
  • Bernd Schierwater
  • Peter J Ratcliffe
  • Christopher J Schofield

Colleges, School and Institutes


The hypoxic response in humans is mediated by the hypoxia-inducible transcription factor (HIF), for which prolyl hydroxylases (PHDs) act as oxygen-sensing components. The evolutionary origins of the HIF system have been previously unclear. We demonstrate a functional HIF system in the simplest animal, Trichoplax adhaerens: HIF targets in T. adhaerens include glycolytic and metabolic enzymes, suggesting a role for HIF in the adaptation of basal multicellular animals to fluctuating oxygen levels. Characterization of the T. adhaerens PHDs and cross-species complementation assays reveal a conserved oxygen-sensing mechanism. Cross-genomic analyses rationalize the relative importance of HIF system components, and imply that the HIF system is likely to be present in all animals, but is unique to this kingdom.


Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalEMBO Reports
Issue number1
Publication statusPublished - Jan 2011


  • Amino Acid Sequence, Animals, Hypoxia-Inducible Factor 1, Molecular Sequence Data, Oxygen, Phylogeny, Placozoa, Procollagen-Proline Dioxygenase, Transcriptional Activation, Von Hippel-Lindau Tumor Suppressor Protein