Figure 1. Transcriptional regulation by oxygen and carbon dioxide.

Metazoan cells have evolved to be capable of sensing levels of physiological gasses in the microenvironment through highly conserved pathways in the control of gene expression. Acute O₂ and CO₂ sensing leads to neuronally mediated changes in processes such as respiratory control and olfactory sensation, respectively. Molecular oxygen (O₂) is sensed by prolyl and aspariginyl hydroxylases, which confer oxygen-dependent instability upon the HIF transcription factor. Activation of this pathway in hypoxia leads to the expression of adaptive genes. The sensor for regulation of NF-κB-dependent gene expression in response to changes in CO₂ has yet to be defined. However, elevated CO₂ leads to repression of the NF-κB pathway and decreased levels of genes which promote innate immunity and inflammation.