Effects of mutations in the heme domain on the transcriptional activity and DNA-binding activity of NPAS2.

The heme domain of neuronal PAS domain protein 2 (NPAS2), a transcription factor that regulates the mammalian circadian rhythm, has been suggested to act as a sensor for carbon monoxide. To characterize the role of the heme domain in this function, we investigated the effects of PASA domain mutants, in the context of full-length NPAS2, on the transcriptional activity of the mouse Period 1 gene in NIH3T3 cells. Mutation of the endogenous ligand for ferrous heme (H119A or H171A) resulted in remarkably reduced transcriptional activity.