Gene regulation in the vascular endothelium: why epigenetics is important for the kidney.

We now appreciate that the vascular endothelium plays a crucial role in regulating normal blood vessel physiology in the kidney. The gene products responsible are commonly expressed exclusively, or preferentially, in this cell type. However, despite the importance of regulated gene expression in the vascular endothelium, relatively little is known about the mechanisms that restrict endothelial-specific gene expression to this cell type. Even less is known about how gene expression might be restricted to endothelial cells of discrete regions of the kidney, such as the glomerulus or vasa recta. Although significant progress has been made toward understanding the regulation of endothelial genes through cis/trans paradigms, it has become apparent that additional mechanisms also must be operative. Classic models of transcription in vascular endothelial cells, specifically the cis/trans paradigm, have limitations. For instance, how does the environment have chronic effects on gene expression in endothelial cells after weeks or years? When an endothelial cell divides, how is this information transmitted to daughter cells? Chromatin-based mechanisms, including cell-specific DNA methylation patterns and post-translational histone modifications, recently were shown to play important roles in gene expression. This review investigates the involvement of epigenetic regulatory mechanisms in vascular endothelial cell-specific gene expression using endothelial nitric oxide synthase as a prototypical model.