Gas-Driven Transcriptional Regulation

Gene expression in mammalian cells is controlled by environmental and metabolic cues, but little is known about the molecular mechanisms that sense and respond to these cues. Dioum et al. (see the Perspective by Boehning and Snyder) have discovered one intriguing mechanism in a study of NPAS2 (neuronal PAS domain protein 2), a transcription factor implicated in the control of circadian rhythms. NPAS2 was shown to bind heme as a prosthetic group, and the heme, in turn, was shown to function as a gas-regulated sensor. In experiments with purified proteins, carbon monoxide (CO) was identified as a candidate ligand for this sensor. Exposure to CO inhibited the dimerization of NPAS2 with BMAL1, the protein that confers the transcription factor with DNA binding activity. E. M. Dioum, J. Rutter, J. R. Tuckerman, G. Gonzalez, M.-A. Gilles-Gonzalez, S. L. McKnight, NPAS2: A gas-responsive transcription factor. Science 298, 2385-2387 (2002). [Abstract] [Full Text] D. Boehning, S. H. Snyder, Carbon monoxide and clocks. Science 298, 2339-2340 (2002). [Summary] [Full Text]