Figure 8.

Schematic representation of molecular mechanisms by which KDM6B regulates IH-induced HIF-1α transcriptional activation of Nox4. IH-induced HIF-1α binds directly to KDM6B, targeting it to HRE sites in promoters of target genes including Nox4. KDM6B mediates H3K27 demethylation, resulting in HIF-1 transcriptional activity from the Nox4 promoter. HIF-1α-dependent increase in Nox4 mRNA leads to augmented ROS abundance, resulting in elevated catecholamines and hypertension in response to IH. HIF, hypoxia-inducible factor; HRE, hypoxia-responsive element; IH, intermittent hypoxia; KDM, lysine demethylases; Nox4, NADPH oxidases; ROS, reactive oxygen species; TSS, transcriptional start site.