Transcriptional regulation is dependent on layers of interactions between transcription factors and coactivators, controlling the specificity, temporal regulation, and extent to which transcriptional programs are executed. A key issue in the field of transcriptional regulation is to identify structural mechanisms by which transcription factors and coactivators build hierarchical protein assemblies. The basic helix-loop-helix Per-ARNT-Sim domain (bHLH-PAS) family of transcriptional regulators comprises both transcription factors and coactivators, which have different functions despite conserved domain architecture. Within this family, the tandem PAS domains typically mediate dimerization of the transcription factors, while C-terminal transactivation domains facilitate the dynamic interplay between transcription factors and coactivators. However, recent studies have shown that the modular PAS domains play an important role in regulating coactivator recruitment and oligomerization status. In this study, we provide a brief overview of the structural and functional studies that have identified a novel protein interaction interface on PAS domains utilized by both transcription factors and coactivators within the bHLH-PAS family.