The Department of Biomedicine

BBB seminar: Murray L. Whitelaw

Roles of bHLH/PAS transcription factors in development and disease

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Murray L. Whitelaw
School of Molecular and Biomedical Sciences and ARC Centre for the Molecular Genetics of Development, University of Adelaide, Australia

The basic Helix-Loop-Helix / Per-Arnt-Sim (bHLH/PAS) family of transcription factors performs essential functions during early development and also regulates homeostatic mechanisms in the adult. Members of this family include:
a) the Hypoxia Inducible Factors (HIF-1a and HIF-2a proteins), which play a major role in embryonic angiogenesis and adaption to low oxygen stress,
b) the Dioxin Receptor (or Aryl hydrocarbon receptor), a key xenobiotic sensor and mediator of the toxic responses to dioxins and PCBs, and
c) Single Minded (Sim1 and Sim2) proteins, which are important for neurogenesis and postnatal survival via mechanisms which are poorly understood.

The HIF, Dioxin Receptor and Sim proteins all need to heterodimerise with a central bHLH/PAS partner protein, termed Arnt, to form active transcription factor complexes. The PAS domain provides a critical protein interaction surface during dimerisation and in many cases functions as a signal regulated domain. The seminar will discuss the various environmental cues and activation mechanisms that control the above transcription factors and consider the implications of cross coupling between the pathways.