The hypoxia-inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens.
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.
Chemistry Research Laboratory and the Oxford Centre for Integrative Systems Biology, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Christoph
C
Loenarz
Mathew L
ML
Coleman
Anna
A
Boleininger
Bernd
B
Schierwater
Peter W H
PW
Holland
Peter J
PJ
Ratcliffe
Christopher J
CJ
Schofield
D000595:Amino Acid Sequence; D000818:Animals; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology*; D008969:Molecular Sequence Data; D010100:Oxygen / Q000502:physiology*; D010802:Phylogeny; D054909:Placozoa / Q000235:genetics / Q000502:physiology*; D011393:Procollagen-Proline Dioxygenase / Q000502:physiology; D015533:Transcriptional Activation; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000502:physiology
D051793:Hypoxia-Inducible Factor 1; D011393:Procollagen-Proline Dioxygenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D010100:Oxygen