Exposure of ECs to short-term (1 h) or long-term (24 h) hypoxia conditions leads to endothelial dysfunction, partly due to reduced expression of endothelial nitric oxide synthase (eNOS), accompanied by significant decreases in acetylation and methylation levels of histones at the proximal promoter of eNOS.219–222 Mechanistically, during acute hypoxia (1 h), histones H3 and H4 are rapidly evicted from the eNOS proximal promoter. The gene discussed is NOS3; the disease is endothelial dysfunction.