Regulation of gene expression by carbon dioxide

Carbon dioxide (CO(2)) 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 CO(2) within tissues are usually significantly higher than those found externally. Shifts in tissue levels of CO(2) (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 CO(2) levels can impact upon disease progression. Recent advances in our understanding of the biology of CO(2) has shown that like other physiological gases such as molecular oxygen (O(2)) and nitric oxide (NO), CO(2) levels can be sensed by cells resulting in the initiation of physiological and pathophysiological responses. Acute CO(2) 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 CO(2) in the regulation of gene transcription has recently been identified with exposure of cells and model organisms to high CO(2) leading to suppression of genes involved in the regulation of innate immunity and inflammation. This latter, transcriptional regulatory role for CO(2), has been largely attributed to altered activity of the NF-B family of transcription factors. Here, we review our evolving understanding of how CO(2) impacts upon gene transcription.