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The basic helix-loop-helix PER-ARNTSIM (bHLH-PAS) family of transcription factors respond to a wide range of external stimuli to regulate diverse biological processes ranging from development to circadian rhythms. These proteins selectively heterodimerize through relatively well-conserved bHLH and PAS domains, while differences in C-terminal regulatory domains confer opposing activities to either stimulate or repress transcription. The evolution of modular regulatory domains and the ability to selectively dimerize with different subunits within the family allows fine-tuning of gene expression through temporal and tissue-specific expression of bHLH-PAS subunits. The aim of this critical review is to discuss the functional specification through modular domain architecture of bHLH-PAS proteins. Conclusion The modular domain architecture of bHLH-PAS transcription factors plays an integral role in their ability to keep mammals healthy and in tune with their environment.

bHLH-PAS proteins: Functional specification through modular domain architecture