Regulation of gene expression by carbon dioxide

Carbon dioxide (CO2) is a physiological gas found at low levels in the atmosphere and produced in cells during the process of aerobic respiration. Consequently, the levels of CO2 within tissues are usually significantly higher than those found externally. Shifts in tissue levels of CO2 (leading to either hypercapnia or hypocapnia) are associated with a number of pathophysiological conditions in humans and can occur naturally in niche habitats such as those of burrowing animals. Clinical studies have indicated that such altered CO2 levels can impact upon disease progression. Recent advances in our understanding of the biology of CO2 has shown that like other physiological gases such as molecular oxygen (O2) and nitric oxide (NO), CO2 levels can be sensed by cells resulting in the initiation of physiological and pathophysiological responses. Acute CO2 sensing in neurons and peripheral and central chemoreceptors is important in rapidly activated responses including olfactory signalling, taste sensation and cardiorespiratory control. Furthermore, a role for CO2 in the regulation of gene transcription has recently been identified with exposure of cells and model organisms to high CO2 leading to suppression of genes involved in the regulation of innate immunity and inflammation. This latter, transcriptional regulatory role for CO2, has been largely attributed to altered activity of the NF-κB family of transcription factors. Here, we review our evolving understanding of how CO2 impacts upon gene transcription.